Download BIOL 273 Midterm #1 Notes

BIOL 273 Midterm #1 Notes
Neurophysiology
Introduction

The nervous system is a network of nerve cells linked together to form the rapid
control system of the body

Nerve cells, also called neurons, are designed to carry electrical signals rapidly over
long distances
o
They link together to transfer a signal by passing chemical signals called
neurotransmitters across the small gap between each neuron, called a
synapse
o

Sometimes (more rarely) they are instead linked by gap junctions
Pathways (paths along which these signals travel) are not necessarily linear –
sometimes a signal influences multiple neurons, or many neurons affect one single
neuron
Organization of the Nervous System

Sensory receptors monitor conditions in the internal and external environments of
the body, and send this information through afferent (or sensory) neurons to the
central nervous system

The central nervous system (or CNS) is the integrating center for neural reflexes – it
receives these afferent signals and then decides what to do with it

Then if an action is needed, the signal for this is sent out through efferent neurons
o
Efferent neurons are divided into the somatic motor division (which controls
skeletal muscles) and the autonomic division (which controls smooth and
cardiac muscles, exocrine and some endocrine glands, and some types of
adipose tissue)

Autonomic
neurons are further divided into
sympathetic
and
parasympathetic branches
o
The afferent and efferent neurons form the peripheral nervous system
Cells of the Nervous System

The nervous system is composed primarily of two cell types: glial cells (“support
cells”) and nerve cells/neurons (the basic signaling units of the nervous system)
Neurons are Excitable Cells that Generate and Carry Electrical Signals

The neuron is the functional unit of the nervous system (the smallest structure that
can carry out the functions of a system)
o
SEE FIGURE 8.2, PAGE 242

Neurons have long things (called appendages or processes) sticking out from their
cell body, either dendrites (which receive incoming signals) or axons (which carry
outgoing information)
o
The shape, number, and length of these things vary from neuron to neuron
The Cell Body is the Control Center of the Neuron

The cell body of the nerve is just like a typical cell body

A cytoskeleton extends into the axon and dendrites

The position of the cell body (in relation to the dendrites, etc.) varies with different
kinds of neurons, but almost always it is small (less than 1/10 of total neuron
volume)
Dendrites Receiving Incoming Signals

Dendrites are thin, branched processes that receive incoming information from
neighboring cells

They increase a cell’s surface area

Basically, their job is to receive incoming information and send it to an integrating
region within the neuron (e.g. the nucleus of the cell)
Axons Carry Outgoing Signals to the Target

Most neurons only have one of these

It comes out of a part of the cell called the axon hillock

They can be as long as a meter long, or just a few micrometers long

But along the axon, they branch and form collaterals
o

Each collateral ends in an axon terminal
The functionality of an axon is to transmit outgoing electrical signals from the
integrating center (i.e. nucleus) of the neuron to the end of the axon

The region where an axon terminal meets its target cell is called a synapse
o
The neuron which delivers the signal to the synapse is called the presynaptic
cell
o
The cell that receives the signal is the postsynaptic cell
o
The narrow space between the two cells is the synaptic cleft
Glial Cells are the Support Cells of the Nervous System

Glial cells provide important physical and biochemical support to neurons

They outnumber neurons in the nervous system by 10-50:1

Neurons do not have much outward support, so glial cells provide structural stability
to neurons by wrapping around them
o
They also provide metabolic support to neurons
o
And help maintain homeostasis of the brain’s extracellular fluid by taking up
excess metabolites and K+

The peripheral nervous system has two types of glial cells: Schwann cells and
satellite cells

The central nervous system has four types of glial support cells: oligodendrocytes,
astrocytes, microglia, and ependymal cells
o
Astrocytes are highly branched cells which transfer nutrients between
neurons and blood vessels
o
Microglia are specialized immune cells which reside permanently within the
CNS, and remove damaged cells and foreign invaders
o
Ependymal cells are epithelial cells that create a selectively permeable barrier
between compartments in the brain
o
Schwann cells in the peripheral nervous system and oligodendrocytes in the
CNS support and insulate axons by creating myelin (multiple concentric
layers of phospholipids membrane)

Myelin forms when these glial cells wrap around an axon and they
squeeze out the glial cytoplasm to form membrane layers


SEE FIGURE 8.6, PAGE 247
So a single axon can have up to 500 Schwann cells wrapped around it,
making the myelin sheath

Between these cells there is a very small part the axon
membrane still in contact with the extracellular fluid, called a
node of Ranvier
o
Satellite cells form supportive capsules around nerve cell bodies located in
ganglia
Electrical Signals in Neurons

Nerve and muscle cells are called excitable tissues because they can propagate
electrical cells when ions move across the cell membrane
The Nernst Equation Predicts Membrane Potential for a Single Ion

Membrane potential is the electrical disequilibrium which results from the uneven
distribution of ions across the cell membrane
o
It is affected by two factors:

Concentration gradients of ions across the membrane

Normally,
sodium,
chloride,
and
calcium
are
more
concentrated in the extracellular fluid than in the cytosol
(inside), while potassium is more concentrated in the cell than
in extracellular fluid

Membrane permeability to those ions

Like, since the resting cell membrane is much more permeable
to potassium, it is the major ion contributing to the resting
membrane potential

The Nernst equation gives us the membrane potential which a single ion would
produce if the membrane were only permeable to that one ion

o
It is called the equilibrium potential of that ion
o
SEE COURSE NOTES FOR THE EQUATION
So for example, if we take the Nernst equation and check potassium, we will see a
membrane potential of -90 mV, but we know that a neuron’s resting membrane
potential is -70 mV, so other ions must be contributing to the potential
The GHK Equation Predicts Membrane Potential Using Multiple Ions

Also known as simply the “Goldman equation”, it calculates the resting membrane
potential which results from the contributions of all ions which can cross the
membrane
o
SEE COURSE NOTES FOR THE EQUATION
o
You will notice that the permeability of the membrane to an ion is in the
equation, because it has an effect on how much a single ion will contribute to
the resting membrane potential
Ion Movement Across the Cell Membrane Creates Electrical Signals

The membrane potential of a cell can be changed by either having the potassium
concentration gradient changed (so there is an imbalance, and more potassium has
to move across to correct this) or having ion permeabilities change (so that other
ions can get in on the action, baby!)
o
So like, if a membrane becomes very permeable to Na+, then more will end
the cell and since it is positive, the cell will move down the electrochemical
gradient – this is a depolarization of the cell membrane, and it creates an
electrical signal
o
But hyperpolarization can also occur – like for example if the cell is more
permeable to K+, and it moves out, so we lose positive charge from the cell
and it becomes more negative, or if negative ions from outside move in all of
a sudden

Note that just because a change in membrane potential occurs, it doesn’t mean that
the concentration gradient of the ions changes – because only very few ions have to
move in order for the potential to change
Gated Channels Control the Ion Permeability of the Neuron

The simplest way for a cell to change its ion permeability is by opening or closing
existing channels in the membrane
o

The other, slower, more ghetto method would be to add or remove channels
Most channels only allow one kind of ion through, but sometimes there are
monovalent channels which allow more than one kind of ion to pass

There are leak channels, which spend most of their time being open

On the other hand there are channels which have gates which open or close in
response to particular stimuli
o
Mechanically gated ion channels are found in sensory neurons and open in
response to physical forces such as pressure or stretch
o
Chemically gated ion channels in most neurons respond to a variety of
ligands, such as extracellular neurotransmitters
o
Voltage gated ion channels play an important role in the initiation and
conduction of electrical signals

Some leak channels are actually voltage gated channels which are just
always open in the voltage range of the resting potential

When the ion channels open, ions move in/out of the cell, and this movement of
electrical charge depolarizes or hyperpolarizes the cell, creating an electrical signal

The electrical signals can be one of two basic types:
o
Graded potentials are variable-strength signals which travel over short
distances and lose strength as they travel through the cell
o
Action potentials are large, uniform depolarizations which can travel for long
distances through the neuron without losing strength
Graded Potentials Reflect the Strength of the Stimulus that Initiates Them

Graded potentials are depolarizations or hyperpolarizations that occur in the
dendrites, cell body, or less frequently, near the axon terminals
o

SEE FIGURE 8.7, PAGE 251
They occur when ion channels open or close, causing ions to enter or leave the
neuron

They are called “graded” because their size or amplitude is directly proportional to
the strength of the triggering event

So for example, a chemical or mechanical stimulus could open up sodium channels,
and then sodium ions move into the neuron and electrical energy comes in
o
Then a wave of depolarization spreads through the cytoplasm (just like a
stone thrown in water creates ripples), and this wave is called local current
flow

Graded potentials lose strength as they move through the cytoplasm for two
reasons:
o
Current leak – so like, if the initial wave is caused by lots of positive ions
coming in, sometimes as the wave moves, positive ions move back outside,
and the electrical difference becomes lesser
o

Cytoplasmic resistance – the cytoplasm itself resists the flow of electricity
If a graded potential is strong enough, eventually it will reach the area of the neuron
called the trigger zone
o
For efferent neurons and interneurons, the trigger zone is the axon hillock
and the very first part of the axon (called the initial segment)
o
For afferent neurons, it is immediately adjacent to the receptor, where the
dendrites join the axon

In the trigger zone, there is a high concentration of voltage-gated Na+ channels
o
So if the current gets here and the membrane here is depolarized to a level
called the threshold voltage, then these channels open and we start an action
potential
o
If the depolarization (current) is not strong enough though, then nothing
happens

So, a graded potential that depolarizes the cell and causes it to fire an action
potential is called an excitatory postsynaptic potential (ESP)

But there are also graded potentials that are hyperpolarizing, and it moves the
membrane farther away from the threshold value, and these are called inhibitory
postsynaptic potentials
Action Potentials Travel Long Distances Without Losing Strength


Action potentials (also called spikes), differ from graded potentials in several ways:
o
All action potentials are identical (i.e. not varied strengths)
o
They do not diminish in strength as they travel through the neuron
The action potential does not even depend on the graded potential which triggered
it!
Action Potentials Represent Movement of Na+ and K+ Across the Membrane

Action potentials are changes in membrane potential that occur when voltage-gated
ion channels open, altering membrane permeability to sodium and potassium
o
SEE FIGURE 8.9, PAGE 253 – UNDERSTAND THIS FIGURE, IT WILL SAVE YOUR
LIFE!
Na+ Channels in the Axon Have Two Gates

The voltage gated Na channel has two gates to regulate ion movement, rather than a
single gate

These gates are called activation and inactivation gates, and they flip-flop back and
forth to open and shut the Na channel
o

SEE FIGURE 8.10, PAGE 254
When the neuron is at its resting membrane potential, the activation gate is closed
and no Na moves through the channel, and the inactivation gate is still open (it is
like a ball-and-chain amino acid sequence)

But when the cell membrane in the area depolarizes, the activation gate opens, and
now Na can move into the cell because the inactivation gate is open from before

And the cell now gets even more depolarized! And as long as it still is depolarized,
the activation gates remain open – this is called a positive feedback loop

But then, the second gate breaks this loop by closing
o
This happens 0.5 milliseconds after the activation gate opens – so basically,
the activation gate opens then the inactivation gate closes 0.5 milliseconds
afterwards, so during that little time, the Na can move into the cell
o

Enough Na moves in to make the rising phase of the action potential
The neuron repolarizes as K+ moves out…
Action Potentials will not Fire During the Absolute Refractory Period

The fact that the Na channel is double gated plays a large role in the thing we call
the refractory period, which is the span of time for 1 millisecond after an action
potential has begun that no other action potential may occur, regardless of how
large the stimulus is

This period is called the absolute refractory period, and it represents the time it
takes for the Na gates to get to their original “starting positions”, from where they
can open again and let more Na into the cell


This means that:
o
Action potentials cannot move backward!
o
And the rate at which signals can be transmitted down a neuron is limited
We also have a relative refractory period after the absolute refractory period, which
is when a stronger-than-normal depolarizing graded potential is needed to bring
the cell to the threshold for an action potential
o
This is partially because during this time, the K+ channels are still open (for
repolarization of the cell as potassium moves out), and so any depolarization
has to be strong enough to overcome that
Stimulus Intensity is Coded by the Frequency of Action Potentials

So, remember how every action potential is identical to every other action potential
for a given neuron?
How do we transmit information through action potentials,
then?
o
We communicate information through the frequency with which the action
potentials occur
o
So, the stronger the graded potential, the higher the frequency of the many
action potentials fired as a result of this graded potential
Action Potentials are Conducted from the Trigger Zone to the Axon Terminal

The movement of an action potential through the axon at high speed is called
conduction

Conduction is the flow of electrical energy from one part of the cell to another in a
process that makes sure that any energy lost as a result of friction or leakage out of
the cell is immediately replenished

So how does this flow process work? Well…
o
When a graded potential reaches threshold in the trigger zone, we have Na
channels opening…And Na+ enters…
o
Now the cell depolarizes, and all this positive stuff comes in
o
But the positive charge in this area is repelled by the Na+ which has just
entered, and the charge travels farther down the axon, and depolarizes the
region down there!
o
Then the exact same thing happens – the Na+ channels open because of the
depolarization, more Na+ enters, and so on

SEE FIGURE 8.14, PAGE 258
Larger Neurons Conduct Action Potentials Faster

Two key physical parameters influence the speed of action potential conduction:
o
The diameter of the neurons

Current flowing in an axon meets resistance from the membrane, so
the larger the neuron is, the less percentage of the current which is
being slowed down by the membrane
o
Resistance of the neuron membrane to current leak out of the cell

See next section
Conduction is Faster in Myelinated Axons

An unmyelinated axon has low resistance to current leak because the entire axon
membrane is in contact with the extracellular fluid, and so there are lots of ion
channels which the current can leak through
o

SEE FIGURE 8.17, PAGE 260
But myelinated axons limit the amount of membrane in contact with the extracellular
fluid

As an action potential moves down an axon, the signal is “refreshed” every so often
to compensate for current loss from the cell
o

Na channel open, and sodium entry reinforces the depolarization
So, in myelinated axons, this only happens at the nodes of Ranvier, where the axon
membrane is “directly accessing” extracellular fluid – and so it seems like the action
potential is jumping from node to node – this is called saltatory conduction

So, to explain the title of this section, conduction is more rapid in myelinated axons
because when you’re having channels open all the time (as is the case with
unmyelinated axons), the signal travels slower because opening the channels takes
time
o
But myelinated axons only have channels open at the nodes of Ranvier, and
so it goes much faster
Cell-to-Cell Communcation in the Nervous System

The specificity of neural communication depends on several factors: the signal
molecules secreted by neurons, the target cell receptors for these chemicals, and the
anatomical connections between neurons and their targets, which occur in regions
known as synapses
Information Passes from Cell to Cell at the Synapse

A synapse is the point at which a neuron meets its target cell

There are three parts of the synapse:

o
The axon terminal of the presynaptic cell
o
The synaptic cleft
o
The membrane of the postsynaptic cell
Synapses are classified as either electrical or chemical, depending on the type of
signal that passes between cells
o
Electrical synapses pass an electrical signal or current directly from the
cytoplasm of one cell to another through gap junctions

Information can flow either way

Electrical synapses are mostly in the CNS

The primary advantage of these things are the rapid conduction of
signals from cell to cell
o
Chemical synapses are the vast majority of synapses, and they use
neurotransmitters to carry information from one cell to the next

Neurotransmitter synthesis can take place either in the nerve cell
body or in the axon terminal

Neurotransmitters are “stored” in synaptic vesicles usually located
near the synaptic cleft, just waiting to open and release their contents
Calcium is the Signal for Neurotransmitter Release at the Synapse

The release of neurotransmitters into the synapse takes place by exocytosis
o
SEE FIGURE 8.20, PAGE 264, IT WILL SAVE YOUR LIFE!
Integration of Neural Information Transfer
Neural Pathways May Involve Many Neurons Simultaneously

Sometimes a single neuron branches, and its collaterals synapse on multiple target
neurons – this is called divergence

Or we can have a single postsynaptic neuron having synapses with over 10,000
presynaptic neurons – this n-to-1 input is called convergence
o
So here we have input from multiple sources influencing the output of a
single postsynaptic cell – the response of the postsynaptic cell is determined
by the summed input from the presynaptic neurons

There is spatial summation, when several stimuli arrive at different dendrites of a
single neuron, and they all meet together at the trigger zone to make an action
potential
o

SEE FIGURE 8.26, PAGE 271
Postsynaptic inhibition happens, though, when one of the graded potentials which
enters a neuron is from an inhibitory neurotransmitter (creating an inhibitory graded
potential), and in this case we can have it canceling out the effects of the other
excitatory graded potentials

There is also temporal summation, when we have two graded potentials (could have
arrived from the same presynaptic neuron) but they are so close together in time
that the second contributes to the depolarization of the first, and it is enough to
cause an action potential
Efferent Division: Autonomic and Somatic Motor Control
Introduction

The efferent side of the peripheral nervous system has two divisions:
o
The somatic motor neurons which control skeletal muscles

o
Generally, these things control voluntary movement
The autonomic neurons which control smooth muscle, cardiac muscle, many
glands, and some adipose tissue

Generally, these things control involuntary movement
The Autonomic Division

The reason for the prefix “auto” in this word is because the functions in the
autonomic division are not under voluntary control

The autonomic division is subdivided into sympathetic and parasympathetic
branches
o
The parasympathetic branches are more for “at rest” kinds of processes, like
resting and digesting
o
The sympathetic branch is dominant in stressful situations, like automatically
removing your hand from a fire, for example
Antagonistic Control is a Hallmark of the Autonomic Division

The sympathetic and parasympathetic branches of the autonomic nervous system
together display properties of homeostasis:
o
Maintenance of the internal environment
o
“Up-down” regulation by varying tonic control
o
Antagonistic control
o
Variable tissues responses that result from differences in membrane
receptors

Most internal organs are under antagonistic control, where one autonomic branch is
excitatory and the other branch is inhibitory
o
For
example,
sympathetic
innervation
increases
heart
rate
and
parasympathetic stimulation decreases it
Autonomic Pathways Have Two Efferent Neurons in Series

The sympathetic and parasympathetic branches in the autonomic division share the
same general structure

All autonomic pathways consist of two neurons in series
o
SEE FIGURE 11.4, PAGE 372
o
The first neuron is called the preganglionic neuron, and it originates in the
CNS and projects to an autonomic ganglion outside the CNS
o
Then the preganglionic neuron synapses with the second neuron in the
pathway, the postganglionic neuron
o

Then the postganglionic neuron projects its axon to the target tissue
The autonomic ganglia is where the two efferent neurons synapse, and it is like an
integrating center for preganglionic and postganglionic neurons
o
Divergence even occurs here – one preganglionic neuron can synapse here
with 8 or 9 postganglionic neurons
Sympathetic and Parasympathetic Branches Exit the Spinal Cord in Different Regions

There are two anatomical differences between sympathetic and parasympathetic
branches

o
Firstly, the pathways originate from different places in the CNS
o
The locations of the autonomic ganglia are different as well
o
SEE FIGURE 11.5, PAGE 373
Most sympathetic pathways originate in the thoracic and lumbar regions of the
spinal cord
o
Sympathetic ganglia are found in a chain which runs close to the spinal
column, and then there are long nerves which go to the spinal tissues
o
So that’s why sympathetic pathways have short preganglionic neurons and
long postganglionic neurons

Many parasympathetic pathways originate in the brain stem originate in the brain
stem
o
And parasympathetic ganglia are located on or near their target organs
o
And so we have long preganglionic neurons and short postganglionic
neurons
The Autonomic Nervous System Uses a Variety of Neurotransmitters and Modulators

All autonomic preganglionic neurons release acetylcholine (ACh) onto cholinergic
nicotinic receptors

Most postganglionic sympathetic neurons secrete norepinephrine onto adrenergic
receptors

Most postganglionic parasympathetic neurons secrete acetylcholine onto cholinergic
muscarinic receptors

SEE FIGURE 11.7, PAGE 375
Autonomic Pathways Control Smooth Muscle, Cardiac Muscle, and Glands

The synapse between a postganglionic autonomic neuron and its target cell is called
the neuroeffector junction

Autonomic axons are different from “normal” axons because they have a series of
swollen areas at their distal ends, like beads spaced out along a string

o
These swellings are called varicosities
o
Each of these things contains vesicles filled with neurotransmitters
Basically, the axon branches out at the end and all these branches lie across the
target tissue, and the vesicles release their neurotransmitters into the interstitial
fluid and they diffuse to where the receptors in the tissue are
o

In this way, we a large surface area of tissue
SEE FIGURE 11.8, PAGE 375
The Somatic Motor Division
Introduction

Somatic pathways only have a single neuron that originates in the CNS and projects
its axon to the target tissue, which is always a skeletal muscle

Somatic pathways are always excitatory
A Somatic Motor Pathway Consists of One Neuron

The cell bodies of all the somatic motor neurons are located within the gray matter
of the spinal cord or brain
o
And there is a long single axon projecting to the skeletal muscle target, and
they can be like a meter long!

When the motor neurons get close to their targets, they branch into a cluster of
enlarged axon terminals, also called “boutons”

The synapse of a somatic motor neuron on a muscle fiber is called the
neuromuscular junction
o
SEE FIGURE 11.12, PAGE 382
o
On the postsynaptic side of the neuromuscular junction, the part of the
muscle cell across from the axon terminal is called a motor end plate – a
series of folds which look like shallow gutters

Along the upper edge of each gutter, nicotinic ACh receptor channels
cluster together into an active zone

Between the axon and the muscle, there is a fibrous matrix which
holds everything together
The Neuromuscular Junction Contains Nicotinic Receptors

So this is how the muscle contraction works!
o
Action potentials arrive at the axon terminal and they open voltage-gated
Ca2+ channels in the membrane
o
Calcium diffuses into the cell down its electrochemical gradient and it causes
synaptic vesicles containing ACh to be released
o
Then Acetylcholine diffuses across the synaptic cleft and combines with
nicotinic receptor channels on the skeletal muscle membrane – this causes
the channels to open
o
Now tons of Na comes into the muscle fiber and it depolarizes, triggering an
action potential that causes contraction of the skeletal muscle cell
o
And this makes another action potential which causes the contraction of the
skeletal muscle cell!

So acetylcholine acting on the motor end plate is always excitatory and creates
muscle contraction
o
There is no antagonistic innervation to relax skeletal muscles
Muscles
Introduction


Our muscles have two common functions:
o
Generate motion
o
Generate force
There are 3 types of muscle tissue in the human body
o
Skeletal muscle

o
Attached to bones of the skeleton, they control body movement
Cardiac muscle

Found only in the heart, they move blood through the circulatory
system
o
Smooth muscle

Primary muscle of internal organs and tubes such as the stomach,
urinary bladder, and blood vessels


It influences the movement of material into, out of, or within the body
Skeletal and cardiac muscles are classified as striated muscles because of their
alternating light and dark bands

They only contract in response to a signal from a somatic motor neuron – they
cannot initiate their own contraction, and their contraction is not influenced directly
by hormones

On the other hand, cardiac and smooth muscle have multiple levels of control
o
There is autonomic innervation
o
But then also spontaneous contraction, and endocrine system’s modulation
Skeletal Muscle

They are responsible for positioning and moving the skeleton

The muscles are usually connected to bones by tendons made of collagen
Skeletal Muscles are Composed of Muscle Fibers

A skeletal muscle is a collection of muscle cells, or muscle fibers (just like a nerve is
a collection of neurons)

Groups of muscle fibers that function together and the motor neuron that controls
them are called a motor unit
Muscle Fiber Anatomy

SEE FIGURE 12.3, PAGE 392, IT WILL SAVE YOUR LIFE!

The cell membrane of a muscle fiber is called the sarcolemma, and the cytoplasm is
called the sarcoplasm

The main intracellular structures are the myofibrils – bundles of contractile and
elastic proteins that carry out the work of contraction

Skeletal muscle fibers contain an extensive sarcoplasmic reticulum (SR) – a modified
kind of endoplasmic reticulum which wraps around each myofibril like a piece of lace
o
The SR is just a bunch of longitudinal tubes (which release Ca2+) and the
terminal cisternae, which concentrates and sequesters Ca2+

There is also a network of tranverse tubules (aka t-tubules) which is closely
associated with the terminal cisternae
o
These t-tubules allow action potentials which originate at the neuromuscular
junction to move rapidly into the interior of the fiber – without these things,
action potentials would only move by the positive charge diffusing through
the cytosol, which takes very long
Myofibrils are the Contractile Structures of a Muscle Fiber

Each myofibril is composed of several types of proteins: the contractile proteins
myosin and actin, the regulatory proteins tropomyosin and troponin, and the giant
accessory proteins titin and nebulin

Myosin is the protein that makes up the thick filaments of the myofibril
o
Each myosin molecule is composed of two heavy protein chains that
intertwine to form a long coiled tail and a pair of tadpolelike heads
o
In skeletal muscle, about 250 myosin molecules join together to make a thick
filament

The thick filament is arranged like the myosin heads are clustered at
the ends, and then they are hinged onto a stiff rod, and then at the
end there is just a bunch of tails

Actin is the protein which makes up the thin filaments of the muscle fiber – it is like
a round ball
o
But then, lots of actin molecules polymerize to form a long chain
o
And two of these chains twist together like a double strand of beads, and
voila, we have thin filaments

Usually, the parallel thick and thin filaments in the myofibril are connected by
crossbridges which span the space between the filaments
o
And it’s actually the myosin heads (of the thick filament) which loosely bind
to the thin filaments

So when we have these thin/thick/thin/thick/… sort of things going on, we get a
repeating pattern of alternating light and dark bands

One repeat of this pattern is called a sarcomere, which has the following elements:
o
SEE FIGURE 12.5, PAGE 395
o
Z disks: zigzag structures which serve as the sites for the thin filaments to
attach – basically, the pattern is a Z disk, then the thin filaments, then
another Z disk
o
I band: these are the lightest colored bands on the sarcomere, and it’s a
region occupied only by thin filaments

A Z disk runs through the middle of an I band, so each half of the
band is in a different sarcomere
o
A band: This is the darkest of the bands in a sarcomere, and it takes up the
entire length of a thick filament

At the outer edges of this band, the thick and thin filaments overlap
o
H zone: this is the central region of the A band, and it is only thick filaments
o
M line: this is the attachment site for the thick filaments (like the Z disk for
the thin filaments)


Titin is a protein which does two very important things:
o
It stabilizes the position of the contractile filaments
o
Its elasticity returns stretched muscles to their resting length
Nebulin also helps to align the actin filaments of the sarcomere
Muscle Contraction Creates Force

So these are the major steps leading up to skeletal muscle contraction:
o
Events at the neuromuscular junction convert a chemical signal from a
somatic motor neuron into an electrical signal in the muscle fiber (we talked
about this before!)
o
Excitation-contraction coupling happens, which is when muscle action
potentials initiate calcium signals
o
Then the contraction-relaxation cycle is activated, and we get the sliding
filament theory of contraction – one muscle twitch per contraction-relaxation
cycle
Muscles Shorten when they Contract

Basically, we are talking about the sliding filament theory of contraction, which says
that overlapping muscle fibers of fixed length (the thick and thin filaments) slide
past each other in an energy-requiring process, resulting in muscle contraction
o
The theory says that the tension generated in a muscle fiber is directly
proportional to interaction between the thick and thin filaments
Sliding Filament Theory of Contraction

OK, when a sarcomere is in the relaxed state, we have the following:
o
The I band is long (area with only thin filaments)
o
The A band is long (area with thick filaments, but there are overlapping thin
filaments at either end)

But…when we get contraction, the sarcomere shortens
o
Then thin filaments move “in” – meaning that the Z disks get closer together
o
The I band pretty much disappears (because there is no longer a region
where it is just thin filament) and so does the H zone (the area of the A band
with only thick filament)
o
Note that the A band’s length remains constant though, which shows that it
is the thin filaments sliding to the inside

So how does this work chemically? Well, I’m glad you asked…
o
OK firstly, remember that myosin filaments are the same as thick filaments,
and actin filaments are the same as thin filaments
o
Each myosin head (remember the bag of golf clubs analogy?) has two binding
sites on it: one for an ATP molecule and one for actin

It is in fact called a “myosin ATPase” because it binds ATP and then
hydrolyzes it to ADP and inorganic phosphate, and this releases
energy
o

So, here we go…
The events of the contractile cycle:
o
SEE FIGURE 12.9, PAGE 398
o
The rigor state
o

This is when the myosin heads are tightly bound to an actin molecule

Right now, in the second binding site on the myosin, there is no ATP

So we are stiff at this point
ATP binds and myosin detaches

An ATP molecule binds to the myosin head, and then myosin can no
longer bond to actin, so it releases the actin
o
ATP hydrolysis

The binding site on myosin closes around ATP and hydrolyses it to
ADP and inorganic phosphate
o
Myosin reattaches: weak binding

Now, with the energy which was released when ATP was hydrolyzed,
the myosin molecule rotates and it binds to a new G-actin molecule
which is further “down the line”
o
Phosphate release and the power stroke

Phosphate gets released, and this causes the myosin to rotate back to
its original starting position – and since the actin is still attached, it
causes the actin to move along
o
Release of ADP

Remember when ATP became ADP and phosphate, then we released
phosphate? We still have ADP, but now we release it and we’re back
to step 1, and the actin is again “stiffly bound” to the myosin
Contraction is Regulated by Troponin and Tropomyosin

So if there’s always ATP available, then why doesn’t this muscle contraction stuff
happen all the time?

It’s because there are proteins called troponin and tropomyosin which regulate it

At a basic level, what they do is to prevent the myosin heads from completing their
power stroke

Tropomyosin is an elongated protein polymer which wraps around the actin filament
and partially blocks the myosin-binding sites

And troponin is a calcium-binding protein which controls the position of
tropomyosin

When tropomyosin is in its blocking position, it lets the myosin bind weakly to the
actin, but not strong enough to let it complete the power stroke
o

SEE FIGURE 12.10, PAGE 399
So troponin is actually a complex of 3 proteins associated with tropomyosin
o
When contraction begins, we have one protein of the complex (troponin C)
which binds to calcium
o
This pulls tropomyosin towards the groove of the actin filament and the
myosin-binding sites are now unblocked
o
And when the muscle relaxes, this is when calcium concentrations in the
cytosol decrease so that calcium unbinds from troponin, and then the
troponin-tropomyosin complex returns to its “off” position
o
It is during this time that the filaments of the sarcomere slide back to their
normal positions with the help of titin and elastic connective tissues within
the muscle
Acetylcholine Initiates Excitation-Contraction Coupling

So let’s go back to the neuromuscular junction, where the entire contraction process
starts!

Here are the steps:
o
SEE FIGURE 12.11, PAGE 400
o
Acetylcholine (ACh) is released from the somatic motor neuron
o
ACh initiates an action potential in the muscle fiber
o
The muscle action potential triggers calcium release from the sarcoplasmic
reticulum
o

Calcium combines with troponin and initiates contraction
This combination of electrical and mechanical events in a muscle is called
excitation-contraction coupling

Alright, so here is the detailed breakdown…
o
So the ACh gets released into the synapse and then they bind to ACh
receptor channels, and the channels open
o
So Na goes into the cell and K comes out, but the electrochemical driving
force is stronger for Na, so more of it goes in and the membrane is
depolarized – this creates an end-plate potential
o
The end-plate potential always causes a muscle action potential, and it goes
across the membrane and down the t-tubules, and then it causes calcium
release from the sarcoplasmic reticulum

This works when dihydropyridine (or DHP) receptors in the t-tubule
membrane which are linked to Ca2+ release channels cause the
channel to open
o
Relaxation occurs when the sarcoplasmic reticulum pumps Ca back into its
lumen using Ca –ATPase

Now there is no calcium to bind to troponin, so the muscles relax
Skeletal Muscle Fibers are Classified by Contraction Speed and Resistance to Fatigue

The different groups we classify muscle fibers into are fast-twitch glycolytic fibers,
fast-twitch oxidative fibers, and slow-twitch (oxidative) fibers

Fast-twitch fibers split ATP more rapidly and so they can complete multiple
contractile cycles more rapidly than slow-twitch fibers

The fiber type also affects how long each contraction is – and this is affected by how
fast the sarcoplasmic reticulum can remove calcium from the cytosol (remember why
this is important?)
o
So fast-twitch fibers are good for fine, quick movements like playing the
piano while slow-twitch is better for prolonged contractions like lifting heavy
loads

Another major different between fast and slow twitch fibers is the ability to resist
fatigue
o
Fast-twitch muscle relies primarily on anaerobic glycolysis to produce ATP

o
But this produces lactic acid and so the muscles get tired quickly
Slow-twitch fibers depend primarily on oxidative phosphorylation for
production of ATP

Why do slow-twitch muscles depend on oxidative phosphorylation?

Well, there is this thing called myoglobin, which binds to
oxygen and works as a transfer molecule to help the oxygen
come into the muscle fiber more quickly – so the slow twitch
muscles have a lot of oxygen

Also, slow-twitch fibers have a smaller diameter, so the
distance that oxygen has to travel is less

On the other hand, fast-twitch muscles have a larger diameter and
less myoglobin, which means they run out of oxygen faster
Tension Developed by Individual Muscle Fibers is a Function of Fiber Length

The tension a muscle fiber can generate is directly proportional to the number of
crossbridges formed between the thick and thin filaments

So like if the sarcomere is very long (recall what a sarcomere is), then that means
that the thick and thin filaments aren’t really overlapping all that much
o
So this would mean that the sliding filaments can interact only minimally and
therefore cannot generate much force

But if the sarcomere is at the optimum length, then there is a lot of crossbridge
linkage, and the fiber can generate optimum force

If the sarcomere is too short, then the filaments cannot move very far…
Force of Contraction Increases with Summation of Muscle Twitches

A single twitch does not represent the maximum force that the muscle fiber can
develop

We can increase the force by increasing the frequency with which muscle action
potentials stimulate the muscle fiber

Basically, if we wait a long time between action potentials, then the muscle has time
to relax, but if we don’t wait, then the muscle fiber will not have relaxed completely
when the next stimulus comes, and this results in a more forceful contraction
o

This process is known as summation
If action potentials continue to stimulate the muscle fiber repeatedly at short
intervals, then the relaxation between contractions diminishes so much that we have
something called tetanus, which is the state of maximal contraction
A Motor Unit is One Somatic Motor Neuron and the Muscle Fibers it Innervates

So recall, a motor unit is composed of a group of muscle fibers and the somatic
motor neuron which controls them
o
When the somatic motor neuron fires an action potential, all the muscle
fibers in the motor unit contract

The number of muscle fibers in a motor unit varies, and this is why that is
important:
o
Basically, it’s that within a single motor unit, all the muscle fibers have to
move at the same time
o
So in delicate movements like blinking an eye, if the motor units only have a
few muscle fibers each, then we can activate as many motor units as we want
in order to produce the movement that we want, and so we can get a fine
gradation of movement
o
But more “bulk” movements like walking or standing, the motor units will
have a lot more muscle fibers, and so we don’t have quite that fine of a
gradation
Contraction in Intact Muscles Depends on the Types of Numbers of Motor Units

So, muscles can create graded contractions of varying force and duration because
muscles are composed of multiple motor units of different types


This allows the muscle to vary contraction by:
o
Changing the types of motor units that are active
o
Changing the number of motor units that are responding at any one time
The force of contraction within a skeletal muscle can be increased by recruiting
additional motor units

Basically there is this pool of somatic motor neurons in the central nervous system
(recall that each somatic motor neuron will control one motor unit)

And each of these neurons have different thresholds for activation

So if we start out by sending a weak stimulus into this pool, then only the lowthreshold neurons will get activated
o
These neurons control fatigue-resistant slow-twitch fibers which do not
generate much force

But if we increase the strength of the stimulus, then additional motor neurons with
higher thresholds begin to fire, and the motor units these guys control are fasttwitch fibers which can generate more force

One way that the nervous system avoid fatigue when we have to sustain contraction
for a long time is through asynchronous recruitment of motor units
o
This means that different motor units within a muscle would take turns
maintaining the muscle tension
Mechanics of Body Movement
Isotonic Contractions Move Loads, but Isometric Contractions Create Force Without
Movement

Note that muscles can create force to generate movement and also create force
without generating movement
o
If you do curls with barbells, then you are doing isotonic contractions, which
is any contraction that creates force and moves a load

Also, when you curl the barbell, you are shortening your biceps
muscles, and that is called a concentric action

But when we slowly extend our arms to bring the weight down, we are
lengthening the biceps muscles and this is an eccentric action
o
If we just hold the weights out in front of our body and don’t let them drop,
this is an isometric contraction because we are not generating movement

How can an isometric contraction create force if the length of the muscle does not
change? Good question…
Bones and Muscles Around Joints Form Levers and Fulcrums

SEE FIGURE 12.21, PAGE 411

The body uses its bones and joints as levers and fulcrums on which muscles exert
force to move or resist a load

A lever is a rigid bar that pivots around a point known as the fulcrum
o
So in the body, we have bones as the levers and flexible joints as the
fulcrums
Smooth Muscle
Smooth Muscles are Much Smaller than Skeletal Muscle Fibers

Smooth muscles are small spindle-shaped cells

They do not have specialized receptor regions for neurotransmitters like the motor
end plates in skeletal muscle synapses, so the neurotransmitters just diffuse across
the cell surface until it finds a receptor

Single-unit smooth muscle is called that because all the muscle fibers in the entire
unit function together – they are connected electrically
o
So you can’t increase contraction force by recruiting more units, but instead
you change the amount of Ca2+ which enters the cell

Multi-unit smooth muscle is all the cells which are not linked electrically
o
So each individual muscle fiber needs to be associated with an axon terminal
or varicosity and stimulated independently
Smooth Muscle Filaments are not Arranged in Sarcomeres

So the contractile fibers have a homogeneous appearance under the microscope
because they are not arranged in sarcomeres!

But instead, actin and myosin are arranged in long bundles that extend diagonally
around the cell periphery
o

SEE FIGURE 12.27, PAGE 416
Basically, the long actin filaments attach to protein in the cytoplasm which we call
dense bodies

And then the myosin filaments which are less numerous lie between the long actin
fibers and are arranged so that their entire surface is covered by myosin heads

And remember, the myosin heads is where all the action takes places with the actin
filaments?
o
So now we have a continuous line of them, so the actin can slide for longer
distances, and so smooth muscle can be stretched more but still have
enough overlap to create optimum tension
Phosphorylation of Proteins Plays a Key Role in Smooth Muscle Contraction

OK, so the biggest difference between smooth muscle and skeletal muscle when it
comes to the molecular events of how it really works is the role of phosphorylation
in the regulation of the contraction process

So, a quick summary of what we think happens:
o
SEE FIGURE 12.28, PAGE 417
o
An increase in calcium in the cytosol initiates contraction
o
Calcium binds to calmodulin, which is a binding protein found in the cytosol
(as opposed to troponin)
o
Then we start a cascade of events which end in contraction (as opposed to
having contraction happen immediately)

o
Phosphorylation of proteins is an essential step in there…
o
And we regulate this stuff by regulating myosin ATPase activity
To get a little more detailed…
o
When the calcium binds to the calmodulin, an enzyme called myosin light
chain kinase (MLCK) gets activated, and then myosin ATPase activity is
enhanced, and this is when we get more actin binding and cross-bridge
cycling, which increases muscle tension
Relaxation in Smooth Muscle has Several Steps

SEE FIGURE 12.29, PAGE 418

A lot of these things are in common with skeletal muscle
o
Free Ca2+ is removed from the cytosol

o
Ca2+-ATPase pumps it back into the sacroplasmic reticulum
This causes Ca2+ to unbind from calmodulin, and when this happens, MLCK
inactivates

So the additional step is dephosphorylation of the myosin light chain, which
decreases myosin ATPase activity
Some Smooth Muscles Have Unstable Membrane Potentials

A major route of calcium entry into smooth muscle is entry through voltage-gated
Ca channels
o
But here we don’t even need an action potential to provide the voltage – we
can just have graded potentials which open a few channels, and then Ca
comes into the cell and depolarizes it, and then additional channels are
opened

Also weird is that many kinds of smooth muscle display unstable resting membrane
potentials which vary between -40 and -80 mV
o
Cells that exhibit this cyclic kind of behavior are said to have slow wave
potentials
o
And on occasion, the depolarization reaches threshold and an action
potential is fired

We also have types of smooth muscle with unstable potential, except that the action
potentials happen regularly
o
These are called pacemaker potentials because they create regular rhythms
of contraction, like in some cardiac muscles