1.1 Membrane Structures
All cells are surrounded by membranes, and the membranes for nerve and muscle fibers have
unique properties that allow the selective passage of ions that are key elements in the ability of
these cells to generate action potentials. The surrounding membrane is composed of lipids and
is impenetrable to ions, and thus separates intracellular and extracellular ionic environments.
However, the membrane contains protein channels or pores that allow ions to pass across the
membrane (Figure 1.01). Channels are complex structures made up of multiple subunits that
Membrane channels are selective for which ions can pass through. Some channels are always
open, but are selective (Figure 1.02). Selectivity can be based on ion size (which includes the
size of the hydration sphere) or ion charge (Figure 1.01). Other channels open after undergoing
conformational changes. Conformational changes can occur in response to changes in voltage
across the membrane (depolarization or hyperpolarization) – voltage gated channels. Channels
can serve as receptors, and change conformation after a neurotransmitter attaches to them –
ligand gated channels (Figure 1.02).
1.2 Membrane Biophysics
Extracelular and intracellular ionic environments differ. The selective permeability of the
channels leads to a potential difference across the membrane, the inside negative with respect to
the outside. In the resting state, ions flow down their respective concentration gradients, with
positive sodium charges moving in and positive potassium charges moving out through their
respective channels. Ionic flow down concentration gradients is impeded by intracellular
electrostatic charges due to large negatively charged proteins that can not pass through the
channels. Chloride ions flow freely across the membrane (Figure 1.03). Overall, these forces
lead to a net distribution of ionic charges across nerve and muscle membranes, and a resting
membrane potential that is –70 to 90 mV inside with respect to the outside.
The flow of ions across the membrane would, in time, lead to a reduction of charge separation
and a lower membrane potential. There is an energydependent (ATP) pump that maintains the
concentrations of sodium and potassium (Figure 1.04). Actually, two sodium ions are removed
for every potassium ion returned, and the pump contributes to a small degree to the resting
1.3 Passive Membrane Properties
Passive membrane properties govern how action potentials are propagated down axons and
along muscle fibers. The separation of charges on either side of the membrane also results in
positive ions lining the inside and negative changes lining the outside of the membrane.
Accordingly, the membrane forms a capacitor (Figure 1.05). Intracellular ions offer resistance or
impedence to the flow of additional ions along the length of the fiber. The amount of charge able
to flow down a fiber represents current (Figure 1.05). A high fiber resistance will impede current
flow, with less charge flowing down the fiber and a short membrane length constant. .As an
action potential travels down an axon or muscle fiber, a high membrane capacitance will take
time to charge, leading to a long membrane time constant.
1.4 Ionic and Capacitive Currents
Ionic currents represent the flow of ions across a membrane or down a fiber. Current can cross a
membrane by two mechanisms, capacitive and resistive flow. Capacitive currents represent the
accumulation of ions along one side of a membrane and release of similar ions from the other
side of the membrane, and thus no ions actually flow across the membrane (Figure 1.05).
Resistive flow of ionic current across the membrane occurs through voltagegated channels.
Both types of current flow across a membrane are important, and are usually interconnected
during the generation of action potentials.
Ion flow down a fiber meets resistance from intracellular ions (Figure 1.05). As ions flow, those
near the inner side of the membrane also participate in charging the capacitor, further reducing
the number able to move down the fiber.
It can be useful to view resistance and capacitance as equivalent electronic circuits (Figure
1.05). The potential flow of ions from an action potential can be viewed as a battery. Flow of
positive sodium ions is resisted by flow through channels and the need to charge the
membrane’s capacitance. Internal flow is resisted by intracellular ions.
1.5 Physiologic Adaptations to Enhance Current Flow
It is clear that current flow can be “used up” by high membrane capacitance and high internal
resistance. It also takes time to add charge to the membrane capacitor. These factors can lead
to insufficient flow of ions down the fiber. However, there are several of physiological
adaptations that have evolved that reduce capacitance and resistance and lead to reliable and
rapid conduction along fibers.
Capacitance can be reduced by increasing the thickness of the membrane. This has been
accomplished by adding myelin wrappings to axons, thus reducing capacitance 100 fold (Figure
1.6). This in turn increases conduction velocity along myelinated fibers 50 fold (~50 m/s)
compared to unmyelinated fibers (~ 1 m/s).
Resistance can be reduced by increasing fiber diameter. Myelinated axons are larger (up to 12
microns) compared to unmyelinated axons (up to 1 micron) (Figure 1.6).
1.6 Action Potentials
Action potentials are the basic bioelectric signals recorded in electrodiagnostic studies. Nerve
fiber action potentials are directly recorded in sensory nerve conduction studies. Muscle fiber
action potentials are directly recorded in motor nerve conduction studies and the needle EMG,
but are initiated by nerve fiber action potentials.
1.7 Nerve Fiber Action Potentials
Action potentials represent transient reversals of the voltage across the membrane
(transmembrane potential). Action potentials are initiated by an intracellular depolarization that
opens voltagegated ion channels. The rapid opening of sodium channels allows sodium to flow
down its concentration gradient, causing a reversal of the transmembrane potential with the
inside of the fiber becoming positive (Figure 1.07). There is also a rapid opening of potassium
channels that allows potassium to leave the fiber, thus returning the transmembrane potential so
that the inside becoming negative. However, the potassium channels remain open longer,
resulting in a transient greater degree of intracellular negativity (hyperpolarization). Even
though an action potential results in a reversal of the membrane potential, this is accomplished
by relatively few ions moving back and forth across the membrane.
1.8 Continuous Conduction Along Unmyelinated Fibers
There is an even distribution of voltagegated sodium and potassium channels along the fiber in
unmyelinated nerve fibers. The action potential travels down the fiber in a selfregenerating
manner by continuously depolarizing the membrane ahead. Similarly, there is a following
repolarizating process. The distance along the nerve between the leading depolarization that
initiates the action potential and the following repolarization depends upon the passive
membrane properties, with fiber diameter being the largest determinant. In unmyelinated fibers,
the distance is approximately 20 mm long. Conduction in unmyelinated fibers is slow, < 1 m/sec
because of the time needed to charge the membrane capacitance and depolarize the membrane
Conduction speed can be increased by reducing the internal resistance of the nerve fiber. Low
resistance allows greater ionic current to reach resting membrane along the fiber. This can be
accomplished by increasing the diameter of the nerve fiber. However, there are limitations on
the size of an axon. Another approach is to reduce membrane capacitance. Low capacitance
allows less ionic current to be used to charge the capacitor and more charge can be used to
depolarize the membrane.
1.9 Saltatory Conduction Along Myelinated Fibers
Both approaches are used in myelinated fibers were axon diameters are up to 10x larger than
unmyelinated fibers (Figure 1.06). However, the greatest increase in action potential conduction
velocity is achieved by decreasing capacitance through increasing the effective membrane
thickness with layers of myelin. Myelin wrappings are elongations of Schwann cell membrane
and are arranged in segments along the nerve fiber. The myelin wrappings of Schwann cells do
not abut against each other, and there is are spaces between them called nodes of Ranvier.
Internode lengths vary in a linear fashion with the diameter of the fiber, and range between 0.5
and 1.0 mm long. There is a high concentration of voltagegated sodium channels under the
nodes of Ranvier (Figure 1.09). Since capacitance is low along the internode region, very little
ionic current generated by an action potential is lost charging the capacitance, and the ionic
current travels quickly to the next nodal region. At the node, the degree of depolarization is
sufficient to open the sodium channels and slightly later the potassium channels, and the action
potential is regenerated. Thus, the action potential currents “jump” from node to node at
conduction velocities of 5060 m/s, in contrast to continuous conduction of the action potential
along unmyelinated fibers at conduction velocities up to 1 m/s. However, it should be
understood that although the action potential ionic currents are regenerated at the internodes, the
total wave of depolarization and repolarization moves down the fiber in a continuous manner.
The wave length includes the time sodium and potassium channels remain open, and spans the
length of 3060 internodes (Figure 1.10).
1.10 Conduction Along Whole Nerves
Thus far, the propagation of action potentials considered above represents conduction in single
unmyelinated and myelinated nerve fibers. Routine nerve conduction studies involve the
summated potential from all fibers of a whole nerve. Unmyelinated fibers are much more
numerous than myelinated fibers (Figure 1.06), but they contribute little to the compound action
potential. This is due to their very small individual fiber action potential amplitudes and the fact
that very slow conduction velocities places them behind the arrival of the high amplitude
myelinated fiber action potentials.
1.11 Sensory Nerve Action Potential
With sensory nerve recordings, the whole nerve is electrically activated and the compound
action potential represents the sum of 2000+ nerve fiber action potentials, and is called the
sensory nerve action potential (SNAP) (Figure 1.12). Since each nerve fiber potential is small in
amplitude, the sum is in the microvolt (µV) range.
1.12 Compound Muscle Action Potential
With motor nerve recordings, the whole motor nerve is also electrically activated, but the
recorded response represents the muscle fiber action potentials. There are 100+ nerve fibers
innervating a muscle, and each motor axon branches within muscle and innervates 100 to 1000+
muscle fibers. Thus, the compound action potential represents the sum of 10,000 to 100,000+
muscle fibers action potentials, and is called the compound muscle action potential (CMAP)
(Figure 1.13). Action potentials from muscle fibers are larger in amplitude, and the sum is in the
millivolt (mV) range.
1.13 Temporal Dispersion
Myelinated fibers have a range of fiber diameters reflected in a range of conduction velocities,
and hence the arrival of individual nerve fiber action potentials at the recording electrode will be
spread over time. This is represented in nerve conduction studies as temporal dispersion of the
SNAP and CMAP waveforms. A helpful analogy is to consider action potentials as a group of
runners that includes fast 6minute milers, slow 7 minute milers, and a range of runner running
at speeds in between. Thus, in a 1mile race there will be a 1minute temporal dispersion of the
group crossing the finish line, and in a 10mile race there will be a 10minute dispersion at the
1.14 SNAP Temporal Dispersion
The duration of a single nerve fiber action potential is short (approximately 1 msec) and the
range of conduction velocities is fairly broad (approximately 25 m/s). The negative peak voltage
of late arriving action potentials will occur well after the negative peak of the early arriving action
potentials, and phase cancellation will reduce the amplitude of the summed SNAP (Figure 1.14).
The effects of temporal dispersion will be magnified with conduction over greater distances. For
the SNAP, the effects of temporal dispersion over routine distances will reduce the amplitude by
50% or more.
1.15 CMAP Temporal Dispersion
In motor nerve conduction studies, the duration of a motor unit action potential is long
(approximately 4 ms) and the range of conduction velocities of the nerve fibers is short
(approximately 13 m/s). The negative peak voltage of the late arriving action potentials will
occur close to the negative peak of the early arriving action potentials, and phase cancellation
will reduce the amplitude of the summated CMAP to a relatively little degree (Figure 1.15). The
effects of temporal dispersion will be relatively little affected by conduction over greater
distances. For the CMAP, the effects of temporal dispersion over routine distances will reduce
the amplitude by less than 10%.
Composite figure illustrating several aspects of membrane function. A: Representation of lipid
bilayer membrane with ion channels piercing membrane. B: Protein subunits that make up ion
channel and aspects of pore selectively based on hydrated ion size. C: Effect of membrane
impermeability separating ionic charges, with inside negative.
Mechanisms of altering ion channel permeability. A: Permeability based on hydrated ion size.
B: Permeability based on change in transmembrane potential leading to change in conformation
or charge within the channel (voltagegated channel). C: Permeability based on ligand
interaction causing conformational change within the channel (ligandgated channel).
Diagram showing effects of selective membrane ion permeability and distribution of ions
influenced by their concentration gradients and electrostatic forces. Outward potassium (K +
movement down its concentration gradient countered by electrostatic forces from large
impermeable protein cations (A +
). Sodium (Na +
) ions restricted by size. Membrane freely
permeable to chloride (Cl +
) ions. Net effect is intracellular negativity.
Equivalent membrane circuit. Top: Ion channels and sodiumpotassium pump. Bottom: Driving
force (battery) and channel permeability (resistance) for sodium, chloride and potassium, and the
Composite figure showing passive membrane properties and equivalent membrane circuit. Top:
Injection of current at left depolarizes inside of nerve fiber. There is a distribution of positive
charges along the inner membrane surface due to capacitance, liberating positive charges along
the outer membrane surface (capacitive current). Positive charges used locally for capacitive
current results in fewer charges available farther along the fiber. There is resistance to flow of
charge down the middle of the fiber (axial resistance). Bottom: Equivalent circuit showing
parallel membrane resistance and capacitance and series axial resistance.
Composite figure showing photomicrograph of myelinated fibers and clusters of unmyelinated
fibers, and histogram of the relative numbers and diameter distributions of myelinated (dark
lines) and unmyelinated fibers (lighter lines).
Ionic currents and membrane potential changes during the action potential. A: Top curves show
initial inward depolarizing sodium current and later outward repolarizing potassium current.
Bottom shows opening of individual channels and summed opening of several channels that lead
to the net inward currents. B: Net sodium and potassium currents as they produce the action
potential (dashed lines).
Action potential waveform propagating along unmyelinated fiber showing long wavelength.
Distribution of sodium channels (gNa) which are high at nodes of Ranvies and potassium (gK)
channels which are high at internodes and sodium currents along a myelinated axon.
Action potential waveform propagating along a myelinated fiber showing long wavelength.
Montague showing how a single nerve fiber action potentials (A) can be modeled to form the
compound nerve action potential. A: Single action potential. B: Nerve fiber diameter histogram.
C: Model of single fiber action potentials (inset) summed based on their conduction velocities.
Model of individual sensory nerve fiber action potentials summating to form sensory nerve action
Model of individual muscle nerve fiber action potentials activating muscle fiber action potentials
summating to form compound motor action potential (CMAP).