03 Membrane and Action Potentials
Nervous system:
 is a communication system, in which messages are received, processed, and transmitted
o These messages are electrical signals, or impulses
o The basis of these signals is the action potential
 Action potentials result from the movement of ions across cell membranes
 Cell Transport
1. Lipid-soluble molecules move freely—by simple diffusion and never requiring energy
2. Water-soluble molecules (polar, charged molecules) require cell transport—generally a
membrane transport protein
 All cells use membrane transport proteins to selectively modify the ionic
composition of their internal environment
 fall into two major categories:
1. Carriers bind the solute and undergo conformational changes to transfer the solute
across the membrane
2. Channels interact with the solute to be transported weakly—and transport of
solutes is faster than through a carrier (this is key in creating action potentials)
Sodium and potassium
 the most important ions involved in the action potential—cross the cell membrane in two
general ways
1. K+ and Na+ “leak” channels: always open, permitting the free passage of ions
2. K+ and Na+ voltage-gated channels: open or close in response to changes in
membrane voltage
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Na+-K+ pump (or ATPase): The concentration gradients of Na and K across the membrane are established by a
membrane transport protein, an enzyme known as the
o Na+-K+ pump—a carrier present in all cell membranes—is the underlying reason for action potentials
o For every two potassium ions pumped into the cytosol, the Na+-K+ ATPase pumps three sodium ions
out, thus accomplishing two things:
1. Chemical concentration gradients for both sodium and potassium
2. Excess of positive charges removed from the cell, making the inside of the cell slightly negative
Ionic Gradients
 Cells use ionic gradients to perform two main functions
1. Ionic gradients drive many types of cellular transport processes
2. Ionic gradients make possible electrical excitability
a. Cells—neurons and muscle fibers—use to create electrical signals
b. Their ability to create, and conduct electrical impulses makes them excitable cells
Basic Electric Principles
 The difference in charge between two points is electric potential (or potential), and is measured in volts
o This potential establishes an electromotive force, which potentially lead to current—flow of charged
particles between the two points
o In an electrical circuit, the charged particles are free electrons
 Virtually all cells have a potential across their membrane—in a cell, is known as membrane potential
o Unlike batteries, cells establish this potential using ions, not free electrons—thus in a cell, current
involves the flow of ions, not free electrons
o Moreover, the body uses the current of ions to relay a message, not do work per se
 The first step in creating potential across a cell membrane is to establish an unequal distribution of
electrolytes in the extracellular fluid (ECF) vs. the intracellular fluid (ICF)
o all cells do this using the Na+-K+ ATPase
o High Na outside the cell, high K inside the cell
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the membrane potential is created by the interacting potentials of all individual ions, inside and outside the cell
The most important contributions to membrane potential come from sodium and potassium ions
Diffusion potential
 the potential created when an ion diffuses down its concentration gradient
o Such diffusion is possible only if channels exist for that particular ion
 build a hypothetical scenario using K+ channels and diffusion of K+ to explain
Equilibrium Potential
 The equilibrium potential is the
continuation of the concept of the diffusion
potential
 It results when the diffusion force driving
the ion (K+ in the following example) down
its concentration gradient) is precisely
countered by the electrical force “pulling”
the ion against the concentration gradient
 The ion is then at equilibrium, it is no longer
moving across the membrane, and the
equilibrium potential is established and a
voltage can be measured or calculated
A: Initially, there is no potential because ions cannot cross the impermeable membrane. However, there is an
imbalance in ion concentration on either side of the membrane
B: If K+ channels are added to membrane, K+ now diffuses down its concentration gradient creating diffusion potential
C: At equilibrium, the diffusion potential is known as an equilibrium potential, which can be measured
 bulk electroneutrality: for any given solution the # of positive charges balances out the number of negative
o This holds true for the cell and the ECF
 Potential across the cell membrane is established by the movement of a very small number of ions (relatively),
and thus bulk electroneutrality is not disrupted
o Overall, the cell remains neutral and the potential only occurs around the membrane

equilibrium potentials can be calculated for any membrane-permeant ion if its concentration (on either side
of the membrane), and charge, are known
o The Nernst equation: formula that relates the numerical values of the concentration gradient to the
electric gradient that balances it
o Concentration inside divided by the concentration outside of the cell multiplied by a constant divided
by valence charge (x/valence charge multiply [intracellular]/[extracellular])
o mainly using ionic concentration values inside and outside the cell—predicts an equilibrium potential
for a particular ion
 in order to calculate a resting membrane potential, the equilibrium potentials of all important
ions, and how easily they can cross the membrane, must be taken into consideration

There are two formulae which calculate resting membrane potential
 the chord conductance equation, and the Goldman equation
Both equations sum individual equilibrium potentials (calculated in the Nernst equation), but each of these
potentials is weighted by conductance (chord), or permeability (Goldman) of the membrane to the ion
 In a pure lipid bilayer—which is extremely resistant to the passage of any polar solute (such as
ions)—resistance is very high, and conductance (the reciprocal of resistance) is very low
o The conductance of the membrane for any given ion is based on its permeability to that ion
 Permeability depends on the presence of sufficient, specific, and open ion channels
 The importance of including a conductance value in the chord conductance equation, since low
conductance for any ion essentially negates their contribution to resting membrane potential
o In most cells (including nerve cells), potassium has the greatest permeability, followed by
sodium—thus only these two ions have a significant contribution to establishing the resting
membrane potential
Leak Channels
 For both sodium and potassium (but
in particular potassium), their greater
conductance is due to leak channels,
which are constitutively open
o
the resting membrane potential of -70 mV is very close to the
equilibrium potential of K+ (-90 mV)
What Makes up the Difference?
(-90 mV vs. -70 mV)
Assume only potassium exiting
Membrane potential would be -90 mV
Factor in some sodium entering
Membrane potential would be -67 mV
Factor in electrogenic action of sodium/potassium pump (-3 mV)
Membrane potential is -70 mV
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The membrane potential can also be measured experimentally using tiny electrodes—one implanted in the
cell, the other in the extracellular fluid (ECF)
o By convention, the ECF is considered to be at zero volts
o In most excitable cells, the inside of the cell is ~55 to 90 mV less than the ECF, thus creating resting
membrane potentials in the range of -55 to -90 mV
Action potentials
 The term action potential, literally refers to the (membrane) potential in action
o all cells have a membrane potential, only certain cells (neurons and muscle cells) have the ability to
cause change (action) to the potential
Depolarization
 Because of the resting membrane potential, all cells are said to be polarized—the interior cell is negative with
respect to the ECF
o Depolarization literally means a decrease in the magnitude of polarization across the cell membrane
 By convention, depolarization is graphically depicted as an upstroke in the membrane voltage
(i.e., the membrane voltage becomes more positive)
 Note that a depolarization of sufficient magnitude is an action potential
Repolarization and Hyperpolarization
 Repolarization refers to the return of the membrane voltage to its resting value (after depolarization)
o Hyperpolarization refers to an increase in the magnitude of polarization across the cell membrane
 Hyperpolarization is graphically depicted as a downstroke in the membrane voltage (i.e., the
membrane voltage becomes more negative)
Ionic Basis of Action Potentials
 An action potential is the result of rapid changes in membrane conductance to sodium and potassium ions
o changes in conductance arise from opening and closing of voltage-gated Na+ and K+ channels
 Note voltage-gated channels are different from K+ leak channels which are open to allow for a
resting membrane potential
o Voltage gated Na channels have two gates and alternate between
 1. Closed. 2. Opened by depolarization, allows Na to enter cell 3. Inactivated: inactivation gate
closed soon after they open
o Voltage gate K channels have one gate and are either open or closed
 Starting in 1: resting state: all gates are closed
then something happens to cause Na to open
 2: depolarization occurs (less negative, more
positive) and Na comes in hard and fast, making the
inside more positive
 3: then the inactivation gate closes and right
around the same time K voltage gated channels open and
K exits the cell and we repolarize the cell to make it more
negative
 4: Some K channels remain open and Na
channels reset which makes the cell hyperpolarize or go a
little too negative
Poisons
 Several known compounds block ion channels
o The tetrodotoxin (TTX) from pufferfish, and scorpion toxin (ScTX) block voltage-gated Na+ channels
o The local anesthetic lidocaine, also blocks Na+ channels, but when carefully dosed can serve as a local
anesthetic, and anti-arrhythmic in the heart
Refractory Periods
 Absolute refractory period
o During this period—which overlaps with most of the duration of the action potential—the cell is
unable to produce another action potential
 The basis for this are the inactivation gates on the Na+ channels
 Relative refractory period
o During this period—which begins at the end of the absolute refractory period—the cell is able to
produce another action potential, but only with greater than normal inward (depolarizing) current
Graded Potentials
 The excitation of neuron is initiated by stimuli, including chemicals, light, heat, mechanical distortion, etc
o not all stimuli result in an action potential
 many stimuli are not strong enough but do result in some degree of depolarization—this is
termed a graded potential
 The degree of depolarization is directly proportional to the strength of the stimulus (hence the name, graded
potential—the potential is equal to the strength of the stimulus)
o As well, graded potentials lose strength as they travel along the nerve cell
 Note however, that action potentials do not lose strength as they propagate

If a graded potential reaches a depolarization threshold, an action potential occurs
o If the threshold is not met, and action potential does not occur (all-or-none response)
 in contrast to graded potentials, action potentials (in a given tissue) all experience the same
degree of depolarization, no matter how strong the stimulus—in other words, once threshold
is met, all action potentials (in a given tissue) exhibit the same electric profile
Propagation of Action Potentials
 To be effective as a signaling mechanism, an action potential must be propagated (transmitted), be it in a
neuron, or a muscle cell
o the action potential itself does not travel, instead, it gives rise to a series of adjacent action potentials
 The net result is a nerve impulse that travels by renewing itself in a type of chain reaction
 In theory, an action potential could arise at any point along a neuron
o In practice, action potentials occur at the axon hillock, where the density of voltage-gated Na+
channels is maximal
o From the hillock, action potentials proceed away from the cell body due to absolute refractory period
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The flow of electrical current along a cylindrical axon has been compared with that in a submarine cable
o The cable uses a core of highly conductive metal and thick plastic insulation to prevent loss of current
to surrounding sea water
 In principle, axons do the same thing
As axon diameter increases, the conduction velocity of action potentials increases because the internal
resistance of the axon is inversely related to the cross-sectional area of the axon
myelination of smaller diameter axons serves to improve the efficiency of impulse propagation
o Myelin sheaths—produced by oligodendrocytes in the CNS, and Schwann cells in the PNS—insulate
axons, making it nearly impossible for ions to cross the cell membrane
 This increase in the resistance of cell membranes forces current (ions) longitudinally down
the axon interior (path of least resistance), thus improving current flow
 Much better than increasing axon diameter
Conduction Velocity
 graded potential is conducted along the bare membrane of dendrites, which have few voltage-gated channels
o the potential cannot renew itself, and weakens over time and distance
 If the graded potential is not strong enough there is no action potential

Continuous conduction occurs in unmyelinated neurons (i.e., sensory neurons to the skin)
o Action potentials renew themselves as if using short, choppy steps, and therefore the propagation of
the impulse is relatively slow but the voltage does not decay
Saltatory Conduction
 The myelination of axons is not continuous, as each myelin sheath-shaped like a tiny jelly roll- separated from
its neighbor by a bare area of axon
o The bare area between myelin sheaths is known as known as the node of Ranvier
 Virtually no current can be lost to the ECF, so current propagates rapidly along the axon
o with great insulation, and no voltage-gated channels along myelinated portion of the axon, the action
potential does decay
 But at the nodes of Ranvier-rich in voltage-gated channels-the action potential renews itself
 Due to the rapid conduction within the myelinated part of the axon, the speed of the impulse in saltatory
conduction may be 100X as fast as in continuous conduction
 minimizes use of energy, which is required to re-establish Na+ and K+ concentration gradients during
repolarization, as action potentials only occur at the nodes
The Synapse
 A neuron never works alone—indeed they are always part of some type of network, communicating with
other neurons, or other cell types, such as muscle
o In order for an electrical impulse to be of value as a signaling mechanism, it must be able to propagate
to a neighboring cell
 occurs at the synapse—an area of apposition between the membranes of two adjacent cells
 The human brain contains upwards of 500 trillion synapses: One neuron can have up to 100,000 synapses
 Synapses greatly enhance our information processing ability: The more synapses the better
 There are two types of synapses
1. Electrical synapses are less common, and less studied than chemical synapses
a. neurons linked by gap junctions, through which ions flow directly from one cell to the next
b. There is no control/integration of information at electrical synapses, however, impulse
information can pass very quickly from cell to cell since there is no delay
i. important in heart and bladder where must be coordinated contraction of all cells
2.
Chemical synapses
a. no direct communication between adjacent cells
b. The separation between the two cells at the chemical
synapse is referred to as the synaptic cleft (the electric
synapse does not have a cleft per se)
c. An electrical impulse from the presynaptic cell is
converted into a chemical signal (neurotransmitter) in
order to cross the synaptic cleft, and then re-converted
into an electrical impulse by the postsynaptic cell
i. The steps involved create a synaptic delay
o
The neurotransmitter released by presynaptic cell has one of two
effects
Inhibitory neurotransmitters hyperpolarize the postsynaptic
membrane, and inhibit action potentials
Excitatory neurotransmitters depolarize the postsynaptic
membrane, and cause action potentials
1.
2.
Acetylcholine (ACh) first neurotransmitter discovered, in a class by itself
o ACh is the only neurotransmitter used in the motor division of the somatic nervous system (at
neuromuscular junctions)
o It is the main neurotransmitter used in the autonomic nervous system
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Presynaptic Cell
o The depolarizing of action potential arriving at the presynaptic terminal causes Ca + channels to open
The rise in Ca++ in the terminal triggers the fusion of neurotransmitter-containing vesicles with the
plasma membrane
All of the neurotransmitter in the vesicle is expelled, it crosses the cleft, and binds to receptors on the postsynaptic
membrane
Postsynaptic Cell
Neurotransmitter binding to receptors on the postsynaptic cell initiates one of two general responses, which will be
discussed shortly
Transmitters act for only a very short time (milliseconds) before dissociating from the receptors
After dissociation, they are rapidly taken back up and recycled by the presynaptic cell, or enzymatically
degraded, or simply diffuse away
o
Types of Receptors
Background
As mentioned previously, the binding of neurotransmitters to postsynaptic cells initiates one of two general responses,
depending on the receptor type on the postsynaptic membrane
Ionotropic receptors—in which an ion channel is an integral part of the receptor—can initiate an action
potential through channel opening
Metabotropic receptors are coupled to G proteins and activate 2nd messenger cascades
Neuromuscular Junction
 The neuromuscular junction (or motor end plate) is a specialized synapse between motor neurons and
skeletal muscle fibers

A nerve is a tough, stringy organ that bundles and conducts hundreds of axons linking the brain and spinal
cord to various organs (such as skeletal muscle)
o Note that nerves carry axons of both motor, and sensory neurons, meaning that impulses travel in both
directions along the nerve
Axon Processes
 Motor neuron axons branch extensively into axon processes near the point of contact with the target muscle
o There may be up to 200 axon processes branching from each axon, and each process innervates just
one muscle fiber
 The axon process contacts the muscle fiber near the middle of the fiber
 At the actual point of contact between nerve and muscle, each axon process undergoes a final
branching into unmyelinated processes referred to as terminal arborizations
o The bulb-shaped endings of the arborizations are boutons
 each bouton forms a separate synapse with the muscle fiber
 At the synaptic clefts of the neuromuscular junction, the neurotransmitter released is always acetylcholine
(ACh)
o if a vesicle fuses with the presynaptic membrane, all ACh is released
 ACh diffuses across the cleft, and on the postsynaptic membrane binds to ACh receptors
 ligand-gated ion channel for both K+ and Na+ (and other ions: it is non-selective)
o
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With the channel domain of the ACh receptor open, both K+ and Na+ diffuse down their concentration
gradients and theoretically drive the membrane potential to ~0 mV—a value between both ions’
equilibrium potentials
End Plate Potential
In practice—because of the influence of other ions which also pass through the ACh receptor—the membrane
depolarizes not to 0 mV, but to ~-50 mV, the end plate potential (EPP)
o The EPP is not an action potential, but a local depolarization strong enough to elicit an action
potential in adjacent areas of the muscle cell membrane
 From there, the action potential propagates through the muscle membrane
action potential in the nerve causes depolarization
voltage gated Calcium channels open flows in
which causes vesicles full of ACh t0 exocytosis out of presynaptic nerve terminal
Ach binds to Ach receptor on muscle
Channel opens up and Na flows into the motor end plate and K flows out of the muscle
End plate potential= depolarization of motor end plate creates an action potential in the muscle
AChE (acetylcholine esterase) degrades Ach and about 50% is recycled in the presynaptic nerve terminal