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Chapter 4 Lecture Notes, page 1
Chapter 4 -Neurophysiology
I. electrical signals
neurons are specialized for rapid electrical and chemical signaling
electrical signals are temporary alterations in the membrane potential
chemical signals are used at synapses
A. changes in membrane potential relative to resting potential (RMP):
1. depolarization
 inside of membrane less negative than RMP
 membrane potential decreases (closer to 0 mV)
 graph: deflection above RMP
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2. repolarization
 inside of membrane becomes more negative until it gets back to RMP (-70 mV)
 membrane potential increases (farther from 0 mV)
 graph: return to RMP following depolarization
3. hyperpolarization
 membrane potential increases (farther from 0 mV)
 inside of cell becomes more negative than RMP
 graph: deflection below RMP
B. graded potentials act as short-distance signals
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trigger event opens chemically or mechanically gated channels
ions go through gated channels, changing the membrane potential
no new channels are opened in the adjacent membrane so the potentials can’t
spread
ions leak back through membrane, membrane potential returns to resting level
the stronger the stimulus, the more ions move and the greater the change in
membrane potential
types of graded potentials include:
1) postsynaptic potentials (EPSPs and IPSPs)
2) receptor potentials
3) end plate potentials
4) pacemaker potentials
5) slow wave potentials
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C. action potentials (AP) act as long-distance signals
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strength of potential does not vary with strength of stimulus
strength of AP is maintained as it is propagated away from site of initiation
1. AP begins once threshold is reached
a. depolarization overshoots 0 mV
b. repolarization returns membrane to RMP
c. after-hyperpolarization (overshoot)
2. threshold potential = voltage at which Na entry becomes self-reinforcing
usually around -50 mV
3. changes in membrane potential occur when ions move through gated membrane
channels:
Na+ influx - depolarization
K+ efflux - repolarization, hyperpolarization
a. channel configurations
Na+ voltage gated channels
closed
K+ voltage gated channels
closed
activated (open)
activated (open)
inactivated (closed and not
capable of opening)
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b. voltage-gated channels are opened and closed by changes in membrane
potential
proteins are sensitive to voltage changes
structure is altered by changes in ion distribution
c. Na+ voltage-gated channel activation mechanism:
all voltage-gated Na+ channels are closed at -70 mV
a stimulus (triggering event) opens some voltage-gated Na+ channels
Na+ diffuses into cell down its concentration gradient
Na+ entry decreases membrane potential, causing more Na+ channels to
be activated
if depolarization reaches the threshold potential, Na+ permeability becomes
600x that of K+
so much Na+ enters the cell that the inside of the membrane becomes
positive (+30 mV)
the inactivation gates slowly block the channels
Na+ stops entering the cell
during repolarization, the Na+ inactivation gate is replaced by the Na+
activation gate
d. K+ voltage-gated channel activation:
stimulus triggers opening of K channels
K+ channels actually open at peak of AP (+30mV)
K+ diffuses out of cell down its concentration gradient
exit of K+ from cell increases membrane potential and causes cell to
become more negative inside
as membrane returns to RMP (-70 mV) the voltage-gated K+ channels
close
(the K+ leak channels stay open)
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slow closure of K+ channels causes after hyper-polarization
e. after an AP, the Na/K pump slowly moves Na+ back out of the cell and K+
back in
so few Na+ and K+ ions actually move during an action potential that the
pump does not have to catch up before the next AP
but eventually the cell has to rest for long enough to have its ionic
balance restored and the Na+ and K+ concentration gradients reestablished
4. propagation of APs
an action potential is stationary but the signal travels along the membrane
a. contiguous conduction in unmyelinated neurons
depolarization occurs at initial active site or triggering zone, usually the
axon hillock
APs are initiated there because it has the highest concentration of Na+
voltage-gated channels
at the edge of the active site, attraction between positive and negative
charges initiates local current flow between the active site and the
adjacent inactive area
local current flow opens Na+ voltage-gated channels in the inactive area,
Na+ flows in and the area depolarizes
simultaneously, the original active area repolarizes
now depolarization has moved along the membrane
this process automatically continues until it reaches the end of the cell
action potentials do not move, they just trigger new action potentials ahead
of themselves in the adjacent membrane
there is no reduction in strength of the potential as it is propagated
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b. saltatory conduction in myelinated neurons
initiated at axon hillock
depolarization causes local current flow between there and the first node of
Ranvier
myelin prevents current leakage, and there are fewer channels under the
myelin anyway
local current flow opens Na+ channels at the first node, Na+ flows into the
cell, and the membrane at the node is depolarized
simultaneously, axon hillock repolarizes
the local current “jumps” over myelin between nodes
now the first node is depolarized and the next one after that is still resting
local current flow between nodes opens Na+ channels at distal node, etc.
this continues until the signal reaches the end of the neuron
saltatory conduction is more rapid because fewer Na+ and K+ channels
have to open and close than in continuous conduction
5. factors affecting velocity
a. fiber diameter
larger diameter – lower resistance to current flow
the less resistance, the faster the AP is propagated
b. myelination increases velocity 50X
not all parts of membrane have to be depolarized
fewer channels have to open and close, saving time
large myelinated fibers
small unmyelinated fibers
120 m/sec
0.7 m/sec
6. refractory periods
a. during the absolute refractory period the membrane is completely
unresponsive
this occurs while the Na+ gates are open or inactivated
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b. during the relative refractory period, only stronger stimuli can initiate an APs
this occurs while some K+ gates are still closing
c. refractory periods assure one-way conduction
prevent local current flow from going backwards
d. refractory periods limit frequency of transmission
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a site has to recover from the last AP before it can transmit another one
the longer the refractory periods, the fewer impulses per second
7. all-or-none
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the membrane responds completely or not at all
it either propagates the AP throughout the membrane or it does not conduct
it at all
stimuli that depolarize the membrane to the threshold cause APs
stimuli that do not depolarize the membrane to the threshold cause graded
potentials (not all-or-none)
8. intensity coding
All APs are alike to the brain, so how does it get information about the stimulus
from the AP?
the stronger the stimulus:
 the greater the frequency of afferent impulses
 the greater the number of neurons that send afferent impulses
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Chapter 4 Lecture Notes, page 8
II. synapse = junction between two neurons
presynaptic neuron causes changes in the membrane potential of postsynaptic
neuron
communication is one-way
A. mechanism of chemical synapses
action potential in presynaptic neuron opens voltage-gated Ca++ channels in
synaptic knob membrane
Ca++ diffuses down its concentration gradient into neuron
Ca++ induces exocytosis of vesicles containing neurotransmitter
neurotransmitter diffuses and binds to a specific postsynaptic membrane receptor
this opens postsynaptic membrane ion channels
ions flow through the postsynaptic membrane, altering its potential (post synaptic
potential)
B. excitatory and inhibitory synapses
not a function of the neurotransmitter
depends on:
 the kind of ion channel opened
 result is depolarization or hyperpolarization
1. at excitatory synapses
neurotransmitter causes depolarization by opening Na channels
net influx of Na causes excitatory post synaptic potential (EPSP)
2. at inhibitory synapses
neurotransmitter causes hyperpolarization by opening either K+ or Cl- channels
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net influx of Cl- or efflux of K+ causes inhibitory postsynaptic potential
3. synaptic delay = time required for impulse to cross one synapse
0.5 to 1.0 msec
the more synapses in a pathway, the longer the delay
C. neurotransmitters
each synapse uses a specific neurotransmitter
each postsynaptic cell may respond to many different neurotransmitters
1. mechanisms of action:
a. channel activation
b. 2nd messengers
2. inactivation
neurotransmitters are rapidly inactivated after they have stimulated the
postsynaptic cell
a. enzymes in the postsynaptic membrane
b. uptake into axon terminal (recycled or destroyed)
c. diffusion
3. neuromodulators are neuropeptides that may be released simultaneously with
neurotransmitters
enhance or depress synaptic function
long-term effects on either pre- or post-synaptic cell
 change level of enzyme for neurotransmitter synthesis
 change level of neurotransmitter receptors
some neuromodulators have different jobs outside the nervous system
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4. effect of drugs and disease
a.
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drugs may alter synaptic function by
changing neurotransmitter synthesis or release
modifying neurotransmitter binding with its
receptor
altering neurotransmitter inactivation
substituting for defective or absent neurotransmitter
b. diseases may be caused by
 lack of neurotransmitter
 abnormal or absent receptors
D. summation
each neuron receives many simultaneous messages, none of which can cause
depolarization to the threshold alone
membrane potential of cell body and dendrites is sum of all signals the neuron
receives at any time (grand post-synaptic potential, GPSP)
if this potential reaches threshold level of axon hillock it causes an action potential
1. temporal summation
summing of several EPSPs occurring very close together in time
second EPSP begins before previous one ends
if enough EPSPs are summed the threshold is reached and an AP is generated
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2. spatial summation
summing of several EPSPs occurring simultaneously so that their effects are
combined
if enough EPSPs are summed, the threshold is reached and an AP is generated
3. cancellation effect
simultaneous EPSPs and IPSPs cancel each other out
III. integration
A. convergence
any neuron may have many other neurons synapsing on it
the neuron converts several incoming signals to a single outgoing signal
this increases sensitivity in the pathway, but it decreases precision
B. divergence
the axon terminals of each neuron branch out and synapse with many postsynaptic
cells
the neuron converts one incoming signal to many simultaneous outgoing signals
this spreads out a signal and amplifies it
I. intercellular communication – extracellular chemical messengers (ligands)
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target cells have receptors specific for ligands
when a ligand binds with its receptor, the physiological activity of target cell is
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altered
signal transduction is the transfer of information from the ligand to the inside of
the target cell
A. signal transduction mechanisms
1. control of chemically-gated ion channels
a. receptor binding site is part of channel
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channel opens when ligand binds with receptor, allowing ions to
enter or leave the cell
b. receptor binding site is in membrane near channel
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ligand binds with receptor in cell membrane, activating a G protein
the G protein moves to the channel and opens or closes it
 in either case, the channel closes when the ligand is removed from its
receptor
 the ions are moved back across the membrane, usually by ion pumps (active
transport)
2. second messenger systems
used when the ligand cannot enter the target cell
a. general steps
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the ligand (called the first messenger) binds to its membrane receptor,
activating a G protein
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the alpha subunit of the G protein activates a membrane effector
protein, usually an enzyme
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the enzyme catalyzes the formation or activation of the intracellular
second messenger
b. the cAMP (cyclic AMP) second messenger mechanism
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the effector protein is the enzyme adenylyl cyclase, which converts
intracellular ATP into cyclic AMP by removing 2 terminal
phosphates
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cAMP activates the intracellular enzyme protein kinase A (PKA)
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Chapter 4 Lecture Notes, page 13
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PKA phosphorylates another enzyme, bringing about an enzyme
cascade that produces the cellular response to the ligand
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cAMP is inactivated by phosphodiesterase (PDE)
cAMP is used as a 2nd messenger in many different cell types – how can it
generate different responses in different cells?
What would happen if the first messenger inhibited adenylyl cyclase?
c. amplification
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cascading amplifies the original signal from the first messenger
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one first messenger can lead to the activation of thousands of enzyme
molecules and millions of product molecules inside the cell
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