Multiple sclerosis (MS) ranks second only to trauma as a
cause of neurologic disability arising in young and middle-
aged adults. It most commonly strikes between the ages of 20
and 50, and twice as often in females as in males. It currently
affects approximately 400,000 Americans and as many as 3
million people worldwide. MS is an autoimmune condition
in which the myelin sheaths surrounding axons in the central
nervous system are attacked and destroyed by antibodies and
cells of the immune system. The loss of insulating myelin
sheaths results in increased leak of potassium through voltage-
gated channels. This results in hyperpolarization and failure
of action potential conduction of neurons in the brain and
spinal cord. Depending upon the location of the affected
neurons, symptoms can include muscle weakness, fatigue,
decreased motor coordination, slurred speech, blurred or
hazy vision, bladder dysfunction, pain or other sensory
disturbances, and cognitive dysfunction. In many patients,
the symptoms are markedly worsened when body temperature
is elevated; for example, by exercise, a hot shower, or hot
The severity and rate of progression of MS varies
enormously among individuals, ranging from isolated,
episodic attacks with complete recovery in between, to
steadily progressing neurological disability. In the latter case,
MS can ultimately be fatal as brainstem centers responsible
for respiratory and cardiovascular function are destroyed.
ADDITIONAL CLINICAL EXAMPLES
Because of this variability, diagnosing MS can be difﬁ cult.
A person having several of these symptoms on two or more
occasions separated by more than a month is a candidate for
further testing. Nerve-conduction tests can detect slowed or
failed action potential conduction in the motor, sensory, and
visual systems, and cerebrospinal ﬂ uid analysis can reveal the
presence of an abnormal immune reaction against myelin. The
most deﬁ nitive evidence, however, is usually the visualization
by magnetic resonance imaging (MRI) of multiple, scarred
(sclerotic) areas within the brain and spinal cord, from which
this disease derives its name.
The cause of multiple sclerosis is not known, but
it appears to result from a combination of genetic and
environmental factors. It tends to run in families and is more
common among Caucasians than in other racial groups.
The participation of environmental triggers is suggested
by occasional clusters of disease outbreaks, and also by the
observation that the prevalence of MS in people of Japanese
descent rises signiﬁ cantly when they move to the United
States. Among the suspects for the environmental trigger is
infection early in life with a virus, such as those that cause
measles, herpes, chicken pox, or inﬂ uenza. There is presently
no cure for multiple sclerosis, but certain drugs that suppress
the immune response have been proven to reduce the severity
and slow the progression of the disease. A variety of effective
drugs and therapies are now available to help MS patients
cope with their speciﬁ c symptoms.
SECTION B SUMMARY
Basic Principles of Electricity
I. Separated electrical charges create the potential to do work,
as occurs when charged particles produce an electrical current
as they ﬂ ow down a potential gradient. The lipid barrier of
the plasma membrane is a high-resistance insulator that keeps
charged ions separated, while ionic current ﬂ ows readily in the
aqueous intracellular and extracellular ﬂ
The Resting Membrane Potential
I. Membrane potentials are generated mainly by the diffusion
of ions and are determined by (a) the ionic concentration
differences across the membrane, and (b) the membrane’s
relative permeability to different ions.
a. Plasma membrane Na
-ATPase pumps maintain low
intracellular sodium concentration and high intracellular
b. In almost all resting cells, the plasma membrane is much
more permeable to potassium than to sodium, so the
membrane potential is close to the potassium equilibrium
potential—that is, the inside is negative relative to the
c. The Na
-ATPase pumps directly contribute a small
component of the potential because they are electrogenic.
Graded Potentials and Action Potentials
I. Neurons signal information by graded potentials and action
II. Graded potentials are local potentials whose magnitude can
vary and that die out within 1 or 2 mm of their site of origin.
III. An AP is a rapid change in the membrane potential during
which the membrane rapidly depolarizes and repolarizes. At
the peak, the potential reverses and the membrane becomes
positive inside. APs provide long-distance transmission of
information through the nervous system.
a. APs occur in excitable membranes because these membranes
contain many voltage-gated sodium channels. These
channels open as the membrane depolarizes, causing a
positive feedback opening of more voltage-gated sodium
channels and moving the membrane potential toward the
sodium equilibrium potential.
b. The AP ends as the sodium channels inactivate and
potassium channels open, restoring resting conditions.
c. Depolarization of excitable membranes triggers an AP only
when the membrane potential exceeds a threshold potential.
d. Regardless of the size of the stimulus, if the membrane
reaches threshold, the APs generated are all the same size.
e. A membrane is refractory for a brief time following an AP.
f. APs are propagated without any change in size from one
site to another along a membrane.