Download General Physiology

General Physiology
K. Bedu-Addo, PhD
Recommended Books
• Review of Medical Physiology- Ganong
• Textbook of Medical Physiology- Guyton & Hall
• Physiology- Berne et al
• Human Physiology- Sherwood
• Human Physiology- Vander et al
Outline
 Levels of organization in the Human
• Chemical level
• Cellular level
• Tissue level
• Organ level
• Organ System level
• Organism
 Body Water
• Total body water
• Body fluid compartments
• Functions of water
• Measurement of body fluid compartments
 Cellular Membranes
• Structure
• Membrane transport
o Diffusion
 Simple diffusion
 Ionic diffusion
 Facilitated diffusion
o Active transport
 Primary active transport
 Secondary active transport
o Vesicular transport
 Endocytosis
 Exocytosis
o Caveolae
o Osmosis
o Filtration
 Homeostasis
o Homeostatic control systems
o Components of a control system
o Strategies for maintenance of homeostasis
 Nervous Tissues
o Nerve Cells
 Types and classification
o Glial cells
 Types
o Resting membrane potential
o Action potential
 Generation
 Propagation
 Properties
Objectives
After going through the general physiology lectures,
you should be able to:
• describe the levels of organization in the Human
• describe how the levels are organized
• identify the main body fluid compartments and
estimate their volumes
• describe the structure and components of plasma
membranes
• describe the mechanisms involved in the transport
of substances across plasma membranes
• outline the principles of homeostasis and their
application in the human
•
•
•
•
list the main subdivisions of the nervous system
describe the main structure of a neuron
name the glial cells and their functions
describe resting membrane potential and how
it is generated
• describe how changes in cell ionic movements
produce an action potential
• explain propagation of an action potential
Physiology:
The study of how the body and its parts function
Levels of Organization in the Human
The arrangement of specialized parts within a living
thing is sometimes referred to as levels of
organization. The human body has many levels of
structural organization.
• The simplest level of organization within the body is
the chemical level, which is composed of atoms and
molecules
• Cells are the next level of organization
 The cell is the smallest structural and functional
unit that exhibits the characteristics of living
things (organisms)
• Tissues:
Tissues are the next level of organization in any multicellular organism.
 Tissues are cells that are similar in structure
and function and usually joined together
 There are four main tissues, these are:
 Epithelial tissue, which covers exposed
surfaces and lines body cavities.
 Connective tissue, which protects, supports,
and interconnects body parts and organs egs
bone, blood, cartilage
 Muscle tissue, which produces movement
 Nervous tissue, which conducts impulses for
internal communication
• Organs are the next level of organization
 organs are different types of tissues that work
together to perform a particular function
• Organ systems are the next level of organization
 An organ system is a group of organs that
work together to perform a major function
 There are 11 organ systems in the human body.
These are:
 integumentary
 skeletal
 muscular
 Nervous
 Endocrine
 Cardiovascular
 Lymphatic
 Respiratory
 Digestive
 Urinary
 Reproductive
• The last level of organization is the Organism
All body systems function interdependently in a
single living human being, the organism
Body Water
Total amount of water in the body is the total body
water (TBW)
 TBW varies with:
• age
 Declines with age: ≈ 73% of the body weight
in infants, ≈ 60% of the body weight in adults
• gender
 55-60% of the body weight in men
 45-50% of the body weight in young women
• degree of obesity
 Correlates inversely with body fat
• the percentage of water in the fat-free tissue
(‘lean body mass’) is remarkably constant at
73%
 Daily fluid intake and output
In steady state water intake= water loss
• Water input
 ingestion
o by drinking (1500 ml/day)
o by eating (500 ml/day)
o by the metabolism of food (400 ml/day)
 water intake depends on
o climate
o habits
o level of physical activity
• Output
 insensible water loss
o lungs
o skin
 sweating
 urine
 feces
 Body Fluid Compartments
TBW is distributed between two major
compartments- intracellular and extracellular fluid
compartments which are separated by cell
membranes
 Intracellular fluid (ICF)
 comprises 2/3 of the TBW
 constitutes about 40% of the body weight
 found in cells of the body
 high in potassium, magnesium ions, phosphate
and organic anions, proteins and low in sodium
and chloride ions
 Extracellular Fluid (ECF)
 comprises the remaining 1/3 TBW
 constitutes about 20% of body weight
 found outside the cells
 low in potassium & magnesium ions and high
in sodium, chloride and bicarbonate ions
 The ECF is further subdivided into three
subcompartments:
o Interstitial Fluid (ISF)
 surrounds the cells
 does not circulate
 comprises about 3/4 of the ECF
 only compartment that declines with age
o Plasma
 circulates as the extracellular component of
blood
 It makes up about 1/4 of the ECF.
o Transcellular fluid
 It is contained within epithelial lined spaces
 set of fluids that are outside of the normal
compartments
 It includes CSF, GIT fluids, bladder urine,
aqueous humor and joint fluid, peritoneal and
pericardial fluids
 constitute about 0.5 to 2 liters
 Composition of Body Fluid Compartments
Ion
Plasma(mmol/L) ICF(mmol/L)
Na+
K+
Ca2+
Mg2+
ClHCO3HPO4 2SulfateProteinate-
143
5
1,3
0.9
103
24
0,4
0,4
1,14
9
135
<0,8
25
9
9
74
19
64
 Functions of H2O
The functions of H2O in human body are vital. It
• transports nutrients and oxygen into cells
• moisturizes the air in lungs
• helps with metabolism
• protects our vital organs
• helps our organs to absorb nutrients better
• regulates body temperature
• detoxifies
• protect and moisturizes our joints
 we cannot function without H2O
Measurement of body fluid
compartment volumes
Measurement based on the dilution principle
Example: if 25 mg of glucose is added to an unknown
volume of distilled water and the final concentration
of glucose after mixing is 0.05 mg/ml, then the
volume of solvent is?
Volume = 25 mg/0.05 mg/ml
= 500 ml
Corrections
Characteristics of Markers
• should be water soluble
• should be measurable
• should remain in the compartment being
measured
• should not alter water distribution
• should not be toxic
• must not be secreted by the body
• must be unchanged in the body
• amount excreted or metabolically degraded
must be measurable
 TBW
measured using heavy watero dueterium oxide
o tritiated water (tritium oxide)
 ECF volume
measured using:
o inulin
o mannitol
o sucrose etc
 Plasma volume
measured either by using:
o radioiodinated human serum albumin (Risa)
o Evans blue
 Interstitial volume
cannot be measured directly
it is the difference between ECF volume and plasma
volume
 ICF volume
cannot be measured directly
ICF volume is obtained by subtracting the ECF volume
from the TBW
 Blood Volume
o makes about 6-8% body weight of a healthy
adult (5 litres)
o contains both ECF and ICF
o Blood volume is determined by using
radioactive isotopes of phosphorus 32P, iron
55,59Fe and chromium 51Cr.
o Tagged red cells are injected intravenously and
blood volume determined by dilution principle
o blood volume can also be calculated from the
plasma volume if one knows the hematocrit (the
fraction of the total blood volume composed of
red blood cells), using the equation:
For example, if plasma volume is 3 liters and
hematocrit is 0.40, total blood volume would be
calculated as
Cellular Membranes
The cell membrane (also called the plasma
membrane, plasmalemma or "phospholipid bilayer")
is a semipermeable lipid bilayer found in all cells. It
• serves as the attachment point for the intracellular
cytoskeleton
• is a highly selective barriers that regulate what
enters and exits the cell
• detects signals
• is involved in cell-cell communication
• helps in cell identity
 Structure
• Thin, pliable, elastic structure
• between 7.5 –10 nm thick
• The cell membrane is a fluid mosaic of lipids,
proteins, and carbohydrates
• the relative amounts of the components depend
on the membrane's location and role in the body
 Lipids
• There are three different major classes of lipid
molecules:
 phospholipids
 cholesterol
 glycolipids
• Different membranes have different ratios of the
three lipids
o Phospholipids
• are the main components of the lipid bilayer
• the membrane lipids are relatively small
molecules with a hydrophilic (phosphate end)
and hydrophobic (fatty acid end) part
• The hydrophobic 'tails' of many phospholipids
align next to, and opposite each other, forming a
bilayer of phospholipid molecules with hydrophilic
'heads' pointing outwards
• The entire membrane is held together by noncovalent interaction of hydrophobic tails
• the structure is quite fluid and not fixed rigidly
in place
• The bilayer is impenetrable to water soluble
molecules and ions
• The right ratio of saturated to unsaturated fatty
acids keeps the membrane fluid at any
temperature conducive to life
• Four groups of phospholipids make up most of
the plasma membrane, these are:
 phosphatidylcholine
 phosphatidylethanolamine
 phosphatidylserine
 sphingomyeline
• phosphatidylinositols are present in small quantities
o Cholesterol
• steroid lipids
• interdigitate between and have same orientation
as the phospholipid molecules
• Reduces membrane fluidity by reducing
phospholipid movement
• provides mechanical stability to the membranes
• decreases membrane permeability to small
water-soluble molecules
• lowers the temperature required for the
membrane to solidify, contributing to fluidity
 Proteins
Membrane proteins are classified into two major
categories ─ Integral and Peripheral proteins
o Integral proteins
 attached to lipids in the bilayer by their
hydrophobic portions
 transmembrane proteins- have hydrophobic
regions that completely span the hydrophobic
interior of the membrane. The hydrophilic ends
of the molecule are exposed to the aqueous
solutions on either side of the membrane
 monotopic proteins- are only embedded into
one side of the cell membrane
o Peripheral proteins
 are not embedded in the lipid bilayer
 completely on membrane surface
 they form ionic and H-bond interactions with
hydrophilic lipid and protein groups
 can be removed with high salt or alkaline
solutions
• Plasma membrane proteins have several
functions
 channels
 carrier proteins
 receptors
 enzymes
 cell adhesion molecules (CAM)
 gap junctions
 desmosomes
 tight junctions
 antigens
 surface recognition
 cytoskeleton contact
 Carbohydrates
• About 3% of the plasma membrane weight is
carbohydrate
• They are usually branched oligosaccharides
with fewer than 15 sugar units
• Some are covalently bonded to lipids, forming
glycolipids
• Most are covalently bonded to proteins, forming
glycoproteins
• the carbohydrate forms a loose coat on the
membrane called glycocalyx
• Face away from cytoplasm (on outside of cell)
• Plasma membrane carbohydrates function in
several different ways
 receptors
 cell adhesion molecules
 surface recognition
 may be involved in immune reaction
 The plasma membrane is asymmetrical
Eg. Intestinal epithelial cell membrane
• Apical surface selectively absorbs materials
 Contains specific transport proteins
• Lateral surface interacts with neighboring cells
Contains junction proteins to allow cellular
communication
• Basal surface sticks to extracellular matrix and
exchanges with blood
 Contains proteins for anchoring
 Membrane Transport
Cell membranes are differentially (or semi-)
permeable barriers separating the inner cellular
environment from the outer cellular (or external)
environment.
• Permeation of particles across cell membranes is
dependant on two properties ─
 the relative solubility of the particle in lipid
 the size of the particle
• Transport across the plasma membrane is governed
by two basic processes. These are:
 diffusion
 active transport
 Diffusion
Diffusion is the spontaneous movement of material
from a region of high concentration to a region of low
concentration
• Diffusion across membranes is either by simple
diffusion or facilitated diffusion
 Simple Diffusion
It refers to a process whereby a substance passes
through a membrane without the aid of an
intermediary such as a integral membrane protein.
• lipid/non polar soluble substances cross cell
membranes readily than water soluble substances
• cell membranes are impermeable to large water
soluble substances
• the direction of movement of non electrolytes is
along a concentration gradient
• Ions are relatively lipid insoluble. Ionic diffusion is
via protein channels in plasma membranes
• ionic diffusion depends on the electrical and
concentration/chemical gradients ie electrochemical
gradient
 Facilitated diffusion eg glucose, amino acids
• Like simple diffusion net flux is down an
electrochemical gradient
• requires a membrane carrier that spans the
thickness of the membrane
• requires no metabolic energy input
• exhibits characteristics of carrier-mediated
transport
 more rapid than simple diffusion
 saturation
 specificity
 competition
 inhibition
 Active transport
• In active transport substances are moved against
their electrochemical gradient
• requires a carrier protein
• requires energy
• exhibits characteristics of carrier-mediated
transport
• Two types ─ Primary and secondary active
transports
 Primary Active Transport
• Utilizes metabolic energy in the form of ATP
eg Na+-K+ATPase, Ca2+ATPase, H+-K+ATPase
 Secondary Active Transport
• indirect utilization of metabolic energy
• This utilizes the energy released during the
passive movement of one substance down its
electrochemical gradient to transport another
substance against a concentration gradient
eg co-transport of Na+ and glucose, cotransport of Na+ and amino acids
There are several types of membrane transport
proteins.
o Uniports
They move one kind of solute across the lipid bilayer
o Cotransport systems
• They work by simultaneously sending two or
more different solutes across the lipid bilayer
• There are two types of cotransport systems –
 symport- the solutes are sent in the same
direction
 antiport- the solutes are sent in opposite
directions.
 Vesicular Transport
• Movement of macromolecules within membranebound vesicles across cell membranes
• The are two main types─ endocytosis and exocytosis
 Endocytosis
Uptake of macromolecules
• There are three types of endocytosis:
 phagocytosis,
 pinocytosis, and
 receptor-mediated endocytosis
• The material to be internalized is surrounded by an
area of plasma membrane, which then buds off
inside the cell to form a vesicle
• Molecule responsible for pinching off is dynamin
• It requires metabolic energy
 Exocytosis
The process by which materials packaged in vesicles
are secreted from a cell when the vesicle membrane
fuses with the plasma membrane
• requires energy
• requires Ca2+
 Osmosis
The passive diffusion of water across a
semipermeable membrane from a region of low
solute concentration to a region of high solute
concentration ie the passage of water from a region
of high water concentration through a semipermeable membrane to a region of low water
concentration.
• Presence of solute results in a decrease in the
chemical potential of water
• osmosis generates a pressure called osmotic/
hydrostatic ('water-stopping') pressure.
• Osmotic pressure is defined as the hydrostatic
pressure required to stop the flow of water
• If the pressure in the compartment into which
water is flowing is raised to the equivalent of the
osmotic pressure, movement of water will stop
• osmotic pressure is dependant on the number of
particles in solution
• If the total osmotic pressure of two solutions are
equal, they are said to be isotonic
• If solution A has a greater osmotic pressure than
solution B, A is said to be hypertonic to B
• If solution A has a less osmotic pressure than
solution B, A is said to be hypotonic to B
• water diffuses rapidly through cell membranes by
utilizing aquaporins- a group of transmembrane
proteins in the membrane
 Filtration
The process by which fluid is forced through a
membrane/barrier because of differences in pressure
on the two sides. The amount of fluid filtered is
proportionate to
• the pressure difference
• surface area of the membrane
• permeability of the membrane
Homeostasis
Maintenance of a constant internal environment
• The concept was created by Claude Bernard
who proposed the principle of the constancy of
the milieu interieur in 1878.
• The term was coined in 1932 by Walter Cannon
from the Greek words homeo (same, like,
resembling) and stasis (to stand, posture).
• the ECF is considered to be the internal
environment
• The essential variables of the internal
environment that are maintained within limits
acceptable are:
 Concentration of oxygen and carbon dioxide
 pH of the internal environment
 Concentration of nutrients and waste products
 Concentration of salt and other electrolytes
 Volume and pressure of extracellular fluid
 temperature
• Homeostasis is continually disturbed by stress
• Much disease results from disturbance of
homeostasis, a condition known as homeostatic
imbalance.
• Homeostasis depends on the action and
interaction of a number of body systems to
maintain a range of conditions within which the
body can best operate.
These organ systems are the:
 integumentary system
 circulatory system
 lymphatic system and immunity
 digestive system
 nervous system
 endocrine system
 reproductive system
 muscular and skeletal systems
 respiratory system
 excretory system
• the nervous system and to some degree the
endocrine system are the main control systems of
homeostasis
• homeostasis allows humans to live in many habitats
Homeostatic Control Systems
Homeostatic control systems are body components
that generate compensatory regulatory responses to
maintain relatively stable conditions of the internal
environment
• they are subject to nervous and endocrine control
• homeostatic control systems have three
components. They are:
o detectors/sensors
o integrating center
o effectors
• Two basic strategies are used by the body to
maintain homeostasis. These are:
 Feedback
 Feedforward
 Feedback Control
The course of a reaction is controlled by the activity of
some of the products of the reaction ie the output
should have some control over the input.
• Feedback control can be either negative or positive
 Negative Feedback
This occurs when a change in a controlled variable
triggers a response that opposes the change
• Homeostasis primarily operates on this principle
• Negative feedback helps to maintain equilibrium
• Disruption of negative feedback can lead to
undesirable results
Positive Feedback
This occurs when a change in a controlled variable
triggers a response that amplifies the change
• Brings about disequilibrium
• Not involved in homeostasis
• At times, makes negative feedback more efficient
 Feedforward Control
This is a response in anticipation of a change in a
controlled variable. The disturbance is suppressed
before it has had the chance to affect the system's
essential variables
• improves the speed of the body’s homeostatic
responses
• minimizes fluctuations in the level of variable
being regulated
Excitable Tissues
These are tissues that are capable of producing
electrical signals when excited. Excitability of cells and
tissues is a basic function of life. Excitable tissues
include:
• Nerves
• Muscles
• Sensory Receptors
 Nerve Cells
The nervous system consists of neurons and glial
cells. Glial cells outnumber the neurons by 1 to 10
 Neurons
Neurons also known as neurones and nerve cells are
electrically excitable cells in the nervous system that
process and transmit information
A typical neuron has all the parts that any cell would
have, and a few specialized structures (soma,
dendrites and axon) that set it apart.
o Soma/cell body
 the metabolic center of the neuron
 It contains the nucleus, which in turn contains the
genetic material in the form of chromosomes
o Dendrites
 extensions from the soma
 they often look like branches or spikes
 taper towards the apex
 the surfaces of the dendrites receive chemical
messages from other neurons
o Axon
 a long slender extension from the soma
 it emerges from the soma at the 'axon hillock’
 it is uniform in diameter
 it conducts electrical impulses away from the
soma
 The distal terminations of axons called
telodendria/synaptic end bulb/terminal buttons
are specialized in releasing neurotransmitters
 Axons may be myelinated or unmyelinated
• myelinated neurons have neurilemma or
sheath of glial cells wrapped around the axon
to form the myelin sheath
• unmyelinated neurons have glial cells but are
without the dense membrane wrapping which
characterizes myelinated neurons
 Classification of neurons
They are often classified according to function,
structure and type of transmitter released
 Functional Classification
Based on the direction of travel of nerve impulse
relative to CNS. Functionally there three broad
categories of neurons. These are:
• Sensory/Afferent neurons
 convey information from tissues and organs
to the central nervous system
• Motor/Efferent neurons
 transmit signals from the central nervous
system to the effector cells
 Has two branches:
o somatic system
o autonomic system, subdivided into:
• sympathetic
• parasympathetic
• Interneurons
 are the neurons that provide connections
between sensory and motor neurons, as well
as between themselves
 The neurons of the central nervous system,
including the brain, are all interneurons
 Structural classification
Based on the number of processes off the cell body.
Structurally there are three classes of neurons
• Unipolar (or pseudounipolar) neurons.
 These have one short process that immediately
divides into two very long processes both of
which are axons
 they are common
 These cells are found in the spinal ganglia of
the spinal nerves (dorsal root ganglia) as well
as in several of the sensory nuclei of the cranial
nerve nuclei. These cells bring sensory
information into the central nervous system
• Bipolar cells
 these cells consist of a single axon and a
single dendrite (two processes)
 they are rare
 These cells are found in the retina of the eye
and olfactory epithelium cells as well as in
several of the cranial nerves
• Multipolar neurons
 they are the most common type
 they have multiple dendritic processes which
give them an irregular shape
 each neuron has only one axon
 examples: spinal motor neurons, pyramidal
neurons, Purkinje cells
 Neurotransmitter secreted
Neurons can also be classified based on their
chemistry - the neurotransmitter(s) they release
o cholinergic neurons
o adrenergic neurons
o peptidergic neurons
o purinergic neurons
o nonadrenergic/noncholinergic (NANC)
 Glial Cells
Glial cells provide support and protection for
neurons.
The four main functions of glial cells are:
 surround neurons and hold them in place
 supply nutrients and oxygen to neurons
 insulate one neuron from another
 destroy and remove the carcasses of dead
neurons (clean up)
• The four types of CNS supporting cells are
 Astrocytes
o they give nutritional support to the CNS
o Form the blood-brain barrier (by holding
together neurons and blood vessel with a
separation into a two-layered structure)
 Oligodendrocytes
o Form the myelin sheath around axons of the
CNS
o Help to hold nerve fibers together
 Microglia
Phagocyte cells that migrate through the CNS
removing foreign matter and degenerated brain
tissue
 Ependymal cells
o Epithelial cells that line the ventricles of the
brain and spinal cord
o form cerebrospinal fluid and aid in its circulation
• The supporting cells of the PNS are:
 Schwann
Form myelin sheaths around peripheral axons
 Satellite cells
Support neurons in the PNS
Resting Membrane Potential
Membrane potential is the electrical potential
difference (voltage) across a cell's plasma
membrane as a result of separation of charges
across the membrane. The potential difference
across a resting cell is the resting membrane
potential of the cell.
• An insignificant fraction of the total number of
charged particles present in the body fluids is
responsible for the membrane potential
• the resting potential has a negative value, which
by convention means that there is excess
negative charge inside compared to outside
• the magnitude varies from -9 mV to -100 mV
• a resting cell is said to be polarized
Measurement of MP
 Generation of the resting potential
Membrane potentials in cells are determined
primarily by three factors:
 the unequal distribution of K+, Na+, Cl-, and
large intracellular anions across the membrane
 the permeability of the cell membrane to those
ions (i.e., ion conductance) through specific ion
channels
 the activity of electrogenic pumps (e.g.,
Na+/K+-ATPase and Ca2+ transport pumps) that
maintain the ion concentrations across the
membrane.
 Two transport proteins are primarily
responsible for the resting membrane potential
 a K+ leak channel (80%)
The membrane of a resting cell is about 5075 times permeable to K+ than it is to Na+
 the Na+/K+ ATPase (ion pump) (20%)
o direct (electrogenic effect)
o indirect (creation of the concentration
gradients)
MP=0
K+
ECF
+
+
+
+
+
+
+
-
K+
K+
AICF
ECF
+
+
+
+
+
+
+
K+
A-
-
ICF
MP=-90 mV
K+
+
+
+
+
+
+
+
-
K+
A-
K+
+
+
+
+
+
+
+
-
K+
A-
• The movements of ions across membranes are
influenced by two energetic factors. These are:
 the concentration gradient
 the electrical potential difference across the
membrane
• For a specific ion, the electrical potential
difference that exactly counterbalances diffusion
due to the concentration difference is called the
equilibrium potential for that specific ion.
• The equilibrium potential can be calculated from
the Nernst equation
where
Ex is the equilibrium potential for ion X
[Xo] is the concentration of X outside the cell
[Xi] is the concentration of X inside the cell
zx is the valence of ion X
R is the gas constant
T is the absolute temperature
F is Faraday's constant
The equilibrium potential for
K+ is -90 mV
Na+ is +60 mV
Cl- is -70 mV
The measured resting membrane potential of a
neuron is -70 mV
The cell's resting membrane potential combines all
relevant ion currents with
 K+ ions figuring most prominently due to their
high resting conductance
 In addition a small number of Na+ ions leak into
the cell.
 The resulting resting membrane potential is thus
slightly lower compared to the EK+ at around -70mV
 The concentration gradient across the
membrane is maintained by the Na+/K+ ATPase
(ion pump)
In the presence of several different ions, resting
membrane potential can be calculated using the
Goldman-Hodgkin-Katz equation:
where
V = The membrane potential
Pion = the permeability for that ion
[ion]out = the extracellular concentration of that ion
[ion]in = the intracellular concentration of that ion
R = The ideal gas constant
T = The temperature in kelvins
F = Faraday's constant
• Increasing the external K+ concentration
decreases the resting membrane potential
• Decreasing the external Na+ concentration has
little effect on the resting membrane potential
Action Potential
• Two types of responses can be elicited if a
nerve cell is stimulated. These are:
o Graded/local/electrotonic/generator potential
o Action potential
• The type of response depends on the intensity
of stimulation.
 Graded Potentials
A non propagating, localized potential difference
across the membrane of a neuron
• it declines with time and distance from the
stimulus point
• elicited by a stimulus of subthreshold strength
• arise mainly in dendrites and cell bodies
• there is no reversal of polarity
• amplitude depends on strength of stimulus;
varies from less than 1 mV to more than 50mV
• typically longer duration, ranging from msec to
several minutes
• may be hyperpolarizing (inhibitory to generation
of action potential) or depolarizing (excitatory to
generation of action potential)
• has no refractory period
• exhibit temporal and spatial summation
 Action Potential
A self-propagating electrical potential difference
produced across the plasma membrane of nerve or
muscle cells when they are stimulated
• an action potential is initiated by a stimulus
above a certain intensity or threshold
• there is a transient reversal of polarity
• arise at trigger zones and propagate along axon
• propagated, thus permit communication over
long distances
• all or none, typically 100 mV
• typically of shorter duration, ranging from 0.5 –
2 msec
• always consist of depolarizing phase followed
by repolarizing phase and then return to resting
membrane potential
• has a refractory period
• not subject to summation
 Phases of the AP
• Latent period
• Depolarization
• Repolarization
• After-hyperpolarization
 Latent Period
Isoelectric interval. Time taken by stimulus to
travel from point of stimulation to the recording
electrode
 Depolarization
A depolarization of adequate rate and threshold
o causes the voltage-gated Na+ channels to open
making the membrane 4-5000-fold permeable
to Na+ and driving the interior potential from -70
mV up to – 55 mV,
o having reached the action threshold, more
voltage-gated Na+ channels open by a positive
feedback effect
o the Na+ influx drives the interior of the cell
membrane up to about +40 mV
o voltage-gated K+ channels also open. Since the
K+ channels are much slower to open, the
depolarization has time to be completed.
 Repolarization
o the Na+ channels show rapid inactivation for
some time, resulting in a significant decrease in
Na+ conductance before closing
o repulsion of Na+ by the positive interior limits
influx of Na+
o prolonged opening of the voltage-gated K+
channels increases K+ conductance and returns
the potential back to the resting level
 After-hyperpolarization
With both the voltage-gated and non-gated K+
channels open, the membrane potential becomes
more negative than the resting potential
The RP is regained by
 closure of the voltage-gated K+ channels
 efflux of K+ through non-gating K+ channels
 restoration of resting ion concentrations by
the Na+-K+ pump
Decreasing the external Na+ concentrations decreases
the size of the AP
 Propagation of APs
• once an AP is generated at one site, it is
conducted along the axon
• conduction is by local current flow
• The new action potential produces local
currents
• positive charges inside the cell spread from the
active site toward negative charges at the
adjacent inactive site
• these attract negative ions away from the
adjacent membrane
• this current flow causes the adjacent region to
depolarize to threshold generating another AP
• the process repeats itself down the length of
the axon, with an action potential regenerated at
each segment of membrane
 Factors affecting speed of propagation of AP
The speed of conduction can be influenced by:
 the diameter of a fiber
 the presence or absence of myelin
 temperature
 Diameter
Increasing the radius of the axon increases conduction
velocity.
• This is explained by the relationship which
states that the internal resistance R is inversely
proportional to the cross-sectional area:
o thus the larger the fiber the lower the internal
resistance
o and thus the greater the conduction velocity
o the conduction velocity in unmyelinated axons
is proportional to the square root of the axon
diameter
o current flow is facilitated in large-diameter
axons because of the high intracellular ion
mobility
 Presence or absence of myelin
Myelination has two effects
o it decreases the leakiness of the membrane to
ions, as a result it’s very difficult for ions to pass
out of the axons except where there is no
myelin- ie at the nodes of Ranvier
o it greatly reduces the ability of the membrane to
store charge ie it reduces membrane
capacitance. As a result there is little
accumulated charge near the membrane to
slow down current flow within the axon
o Both of these features greatly speed up the rate
of propagation of the AP in a myelinated axon
 Temperature
o increasing the temperature increases ion flow
and the probability of the membrane being
polarized
o temperature has large effects on the rate of
increase of Na+ channel conductance and
action potential waveform
o channels open and close more slowly at lower
temperature, and subsequently conduction
velocity is reduced
o conduction slows down in cooled nerves
 Types of conduction
There are two types. These are
• Regular/Continuous conduction
• Saltatory conduction
 Regular conduction
It is a sequential spread of action potential that occurs
in unmyelinated axons
• action potentials are propagated as waves
 Saltatory conduction
A means by which action potentials are transmitted
along myelinated nerve fibers
• depolarization occurs only at the nodes of
Ranvier where membrane resistance is low
• depolarization at one node of Ranvier is
sufficient to elevate the voltage at a neighboring
node to the threshold for action potential
initiation
• action potentials do not propagate as waves,
but recur at successive nodes and in effect
"hop“ along the axon
• saves energy by decreasing the use of sodium-
potassium pumps in the axonal membrane
• faster than regular conduction
 Refractory Period
The period during an action potential when the ability
of the membrane to respond to a second stimulus is
markedly altered
• it limits the number of APs that can be
produced by an excitable membrane in a given
period
• it is a key in determining the direction of AP
propagation
• It is made up of two phases. These are:
 absolute refractory period
 relative refractory period
 Absolute Refractory Period
It is the period during an action potential, when a
second stimulus will not produce a second action
potential no matter the strength of the stimulus
• it corresponds to the period when the
voltage-gated Na+ channels are open or in the
inactivation state
• coincides with the entire duration of the action
potential
 Relative Refractory Period
It is the period during an action potential when
another action potential can be produced, but
only if the stimulus strength is greater than the
threshold stimulus, then gradually by stimuli of
progressively lesser magnitude
• during this period some but not all of the
voltage-gated Na+ channels have returned to
the resting state
• it corresponds to the period when the
potassium channels are open (several
milliseconds)
• it coincides roughly with the period of
afterhypolarization when the membrane
potential becomes transiently more negative
than the normal resting potential
 Accommodation
The property of a nerve by which it adjusts to a
slowly increasing level of stimulus, so that its
threshold of excitation is greater than it would be were
the stimulus level to have risen more rapidly
• both Na+ and K+ channels are involved
• critical number of open Na+ channels required to
trigger an AP is not attained during slow
depolarization
• increased K+ conduction during depolarization
tends to repolarize the membrane
Organization of the Nervous System
The nervous system orchestrates body functions to
maintain homeostasis
• it is made up of neurons and glial cells
 Functions
• controls and coordinates the body functions
• it processes the incoming sensory information
and generate an appropriate motor response to
adjust activity of muscles and glands
• keeps the previous stimuli as the experiences or
memory which guide the animal in future
• coordinates the visceral functions to maintain a
homeostasis in the body
 Divisions
The nervous system is divided into:
• Central nervous system (CNS)
• Peripheral nervous system (PNS)
 CNS
• consists of the brain and the spinal cord
• is the control center of nervous system
interpreting, integrating, and issuing commands
to the other branches of the nervous system
• encased in bone and protected by CSF and the
meninges
 PNS
includes all parts of the nervous system not covered
by bone
• carries out sensory and motor functions
• contains 12 pairs of cranial and 31 pairs of
spinal nerves, and sensory receptors throughout
the body
• has two subdivisions:
o Sensory (Afferent)
o Motor (Efferent)
 Sensory Division
contains sensory receptors and nerves which carry
information to the CNS
 Motor Division
sends information from the CNS to the body´s
effectors ( muscles, organs, and glands )
o Has two subsystems
 Somatic Nervous system
 Autonomic nervous System
 Somatic nervous system
consists of nerves that carry information to
skeletal muscles which control voluntary
movement
 Autonomic Nervous System
consists of nerves that carry information to visceral
organs and glands
o their activities are outside conscious control
o has two branches:
 sympathetic:
fight and flight division
 parasympathetic:
rest and digest division
 The Human Brain
• It is the site of major coordination in the
nervous system
• it contains around 100 billion neurons linked to
up to 10,000 synaptic connections
• weighs about 1.36 kg in adults
• there are four main areas of the brain:
o cerebrum
o cerebellum
o brain stem
o diencephalon
 Cerebrum
• above the diencephalon
• the largest division of the brain
• consists of two sides, the right and left cerebral
hemispheres, which are interconnected by the
corpus callosum
• the hemispheres are covered by a thin layer of
gray matter known as the cerebral cortex
• each hemisphere of the cerebral cortex is
divided into four lobes called:
o occipital
o temporal
o parietal
o frontal
 Frontal lobe
• most anterior, right under the forehead
• controls:
 motor activity and integration of muscle
activity
 speech (left hemisphere)
 thought processes
 Parietal Lobe
• near the back and top of the head
• coordinates afferent information dealing with:
 pain
 temperature
 form/shape
 texture
 pressure
 position
• Some memory functions are also found here
 Temporal lobe
• side of head above ears
• handles:
 dreams
 memory
 emotions
• center for auditory function
• involved in processing language and the
meaning of words
• olfactory function
 Occipital Lobe
• most posterior, at the back of the head
• receives and processes visual information
 Diencephalon
• located between the cerebrum and the midbrain
• contains the:
o thalamus
o hypothalamus
 Thalamus
• large, bilateral egg-shaped mass of gray matter
• serves as the main synaptic relay center
• receives/relays sensory information to/from the
cerebral cortex
 Hypothalamus:
• a collection of ganglia located below the
thalamus
• intimately associated with the pituitary gland
• controls:
 water homeostasis
 temperature homeostasis
 autonomic activities
• links the nervous system to the endocrine
system via the pituitary gland
• acts as an endocrine gland
• regulates appetite
 Cerebellum
• the second largest brain structure
• sits below the cerebrum
• has an outer cortex of gray matter
• has two hemispheres
• receives/relays information via the brain stem
• controls:
 balance/equilibrium of the trunk
 muscle tension
 spinal nerve reflexes
 posture and balance of the limbs
 fine motor control
 eye movement
 Brainstem
• controls the most basic life functions
• it is the base of the brain
• it adjoins the spinal chord
• contains the:
o medulla oblongata
o pons
o mid brain
 Medulla oblongata
Controls:
• heart rate/action
• vasoconstriction/blood vessel diameter
• breathing
• peristalsis
• reflexes such as:
 swallowing
 coughing
 sneezing
 vomiting
 hiccupping
 Pons
Controls:
• breathing
• reflexes such as:
 pupillary reflexes
 eye movements
 Midbrain
Controls
• reflexes such as:
 pupillary reflexes
 eye movements
THE LIMBIC SYSTEM.
The part of the brain that regulates emotion and
memory
• a complex set of structures that lies on both
sides of the thalamus, just under the cerebrum
• it directly connects lower and higher brain
functions
• horseshoe-shaped
• it includes the:
o Thalamus
o Hypothalamus
o Cingulate gyrus
o Amygdala
o Hippocampus
o Basal Ganglia
o the olfactory bulb and other areas of the brain
are considered part of the limbic system
• the limbic system is concerned with emotional
states (such as rage, fear and memory). The
hippocampus, in particular, plays a vital role in
learning and long-term memory
 The Spinal Chord
• a large, nearly circular mass of nerve tissue
which runs along the dorsal side of the body
• links the brain to the rest of the body
• encased in the vertebral column
• the gray matter of the spinal cord consists
mostly of cell bodies and dendrites
• the surrounding white matter is made up of
bundles of interneuronal axons (tracts)
• has two functions:
o provides the two-way conduction routes
to/from (afferent/efferent) the brain
o serves as the reflex center for all spinal
reflexes