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1. Membrane Potential
AA Ramahi and RL Ruff, Case Western Reserve University, Cleveland, OH, USA; and Louis Stokes Cleveland Veterans Affairs
Medical Center, Cleveland, OH, USA
r 2014 Elsevier Inc. All rights reserved.
This article is a revision of the previous edition article by Robert L Ruff, volume 3, pp 69–70, r 2003, Elsevier Inc.
Introduction
An excitable membrane has a stable potential when there is no
net ion current flowing across the membrane. Two factors
determine the net flow of ions across an open ionic channel:
the membrane potential and the differences in ion concen-
trations between the intracellular and the extracellular spaces.
Because cells have negative intracellular potentials, the elec-
trical force will tend to direct positively charged ions (cations
such as sodium, potassium, and calcium) to flow into a cell.
Hence, electrical forces will direct an inward flow of sodium,
potassium, and calcium ions and an outward flow of chloride
ions. The direction of ion movement produced by the ‘con-
centration force’ depends on the concentration differences for
the ion between the intracellular and the extracellular com-
partments. Sodium, calcium, and chloride ions have higher
extracellular concentrations compared with intracellular con-
centrations. The intracellular concentration of potassium is
greater than the extracellular concentration. Concentration
forces direct an inward flow of sodium, calcium, and chloride
ions and an outward flow of potassium ions. The membrane
potential at which the electrical and concentration forces are
balanced for a given ion is called the equilibrium or Nernst
potential for a given ion. At the equilibrium potential, inward
and outward current movements are balanced for a specific
ion due to balancing of the electrical and concentration forces.
For a given cation, at membrane potentials that are negative
compared with the equilibrium potential, ions flow into the
cell, and at membrane potentials that are more positive than
the equilibrium potential, current carried by the specific ion
will flow out of the cell. The direction of current movement for
a specific ion always tends to bring the membrane potential
back to the equilibrium potential for that specific ion. Ex-
amples of approximate equilibrium potentials for ions in
skeletal muscle are shown in Table 1.
The membrane potential represents a balance among the
equilibrium potentials of the ions to which the membrane is
permeable. The greater the conductance of an ion, the more
that ion will influence the membrane potential of the cell. The
principal conductances responsible for establishing the resting
membrane potential are that of chloride, potassium, and so-
dium. Chloride conductance is large in skeletal muscle fibers,
in which it is mediated by skeletal muscle chloride channels.
Peripheral nerve fibers have smaller chloride conductances.
In skeletal muscle, chloride is the dominant membrane con-
ductance, accounting for approximately 80% of the resting
membrane conductance. Chloride channels in skeletal muscle
are unusual in that they are gated by the presence of ions at
the intracellular and extracellular orifices rather than by the
membrane potential. The channel is likely to open when a
chloride ion presents itself. The unique gating properties of
chloride channels result in the chloride ions being distributed
across the membrane in accord with the membrane potential.
Consequently, chloride conductance does not set the mem-
brane potential.
Instead, chloride conductance acts as a brake to make it
more difficult for the membrane to depolarize. Therefore,
chloride conductance provides an important stabilizing in-
fluence on the membrane potential.
The dominant ion in setting the resting membrane
potential is potassium. Potassium conductance accounts for
approximately 20% of the resting membrane conductance in
skeletal muscle and accounts for most of the resting con-
ductance in neurons and nerve fibers. This is primarily
attributable to nongated ion channels, which are made up of
inward rectifier and ‘slow-leak’ channels. Inward rectifier
channels are responsible for maintaining the membrane po-
tential in the absence of an excitation electrical current. It is
the nongated ion channels that are responsible for differences
in the electrical response of various cell types. For example,
neurons, which contain nongated ion channels for potassium,
sodium, and chloride, have a resting membrane potential that
deviates from the calculated Nernst potential for Kþ
(espe-
cially at low concentrations) whereas glial cells, which contain
nongated ion channels for only potassium, have a resting
membrane potential that matches closely with the calculated
Nernst potential for Kþ
.
The small amount of sodium conductance in the resting
skeletal muscle, or nerve membrane, results in the resting
membrane potential being slightly positive or depolarized
compared with the equilibrium potential for potassium
(Table 2). The specific class of potassium channel that deter-
mines the resting membrane potential is the inward or
anomalous rectifier potassium channel. Resting calcium con-
ductance is exceedingly small. Therefore, calcium does not
contribute to the resting membrane potential.
During an action potential, Naþ
channels open and the
dominant membrane conductance is that of Naþ
. Con-
sequently, the membrane potential is approximately the same
as the Naþ
equilibrium potential (Table 2).
Table 1 Equilibrium potentials
Ion Equilibrium potential (mV)
Sodium 65
Potassium 105
Calcium 4100
Chloride 95 (Resting potential)
Resting potential 95
Encyclopedia of the Neurological Sciences, Volume 2 doi:10.1016/B978-0-12-385157-4.00062-2
1034

2. Acknowledgment
This work was supported by the Office of Research and De-
velopment, Medical Research Service of the Department of
Veterans Affairs.
See also: Action Potential, Generation of. Action Potential,
Regeneration of. Impulse Conduction: Molecular Perspectives. Ion
Channels, Overview. Motor Unit Potential. Muscle Contraction;
Overview
Further Reading
Ruff RL (1986) Ionic channels: I. The biophysical basis for ion passage and
channel gating. Muscle Nerve 9: 675–699.
Shapiro BE and Ruff RL (2002) Disorders of skeletal muscle membrane excitability:
Myotonia congenita, paramyotonia congenita, periodic paralysis and related
syndromes. In: Katirji B, Kaminski HJ, Shapiro BE, Preston D, and Ruff RL
(eds.) Neuromuscular Disorders in Clinical Practice, pp. 987–1021. Boston:
Butterworth–Heinemann.
Table 2 Membrane potential under different conditions
Membrane state Dominant
membrane
conductance
Membrane potential
Resting Kþ
Close to Kþ
equilibrium
potential, approximately
95 mV
Peak of action
potential
Naþ
Close to Naþ
equilibrium
potential, approximately
40 mV
Membrane Potential 1035