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SECTION II
Physiology of Nerve & Muscle Cells
The conventional terminology used for the parts of a neuron
works well enough for spinal motor neurons and interneurons,
but there are problems in terms of “dendrites” and “axons”
when it is applied to other types of neurons found in the ner-
vous system. From a functional point of view, neurons generally
have four important zones: (1) a receptor, or dendritic zone,
where multiple local potential changes generated by synaptic
connections are integrated; (2) a site where propagated action
potentials are generated (the initial segment in spinal motor
neurons, the initial node of Ranvier in cutaneous sensory neu-
rons); (3) an axonal process that transmits propagated impulses
to the nerve endings; and (4) the nerve endings, where action
potentials cause the release of synaptic transmitters. The cell
body is often located at the dendritic zone end of the axon, but
it can be within the axon (eg, auditory neurons) or attached to
the side of the axon (eg, cutaneous neurons). Its location makes
no difference as far as the receptor function of the dendritic
zone and the transmission function of the axon are concerned.
The axons of many neurons are myelinated, that is, they
acquire a sheath of
myelin,
a protein–lipid complex that is
wrapped around the axon (Figure 4–2). In the peripheral ner-
vous system, myelin forms when a Schwann cell wraps its
membrane around an axon up to 100 times (Figure 4–1). The
myelin is then compacted when the extracellular portions of a
membrane protein called protein zero (P
0
) lock to the extracel-
lular portions of P
0
in the apposing membrane. Various muta-
tions in the gene for P
0
cause peripheral neuropathies; 29
different mutations have been described that cause symptoms
ranging from mild to severe. The myelin sheath envelops the
axon except at its ending and at the
nodes of Ranvier,
periodic
1-
μ
m constrictions that are about 1 mm apart (Figure 4–2).
The insulating function of myelin is discussed later in this
chapter. Not all neurons are myelinated; some are
unmyeli-
nated,
that is, simply surrounded by Schwann cells without the
wrapping of the Schwann cell membrane that produces myelin
around the axon.
In the CNS of mammals, most neurons are myelinated, but
the cells that form the myelin are oligodendrocytes rather
than Schwann cells (Figure 4–1). Unlike the Schwann cell,
which forms the myelin between two nodes of Ranvier on a
single neuron, oligodendrocytes emit multiple processes that
form myelin on many neighboring axons. In multiple sclero-
sis, a crippling autoimmune disease, patchy destruction of
myelin occurs in the CNS (see Clinical Box 4–1).
The loss of
myelin is associated with delayed or blocked conduction in
the demyelinated axons.
AXONAL TRANSPORT
Neurons are secretory cells, but they differ from other secretory
cells in that the secretory zone is generally at the end of the axon,
far removed from the cell body. The apparatus for protein syn-
thesis is located for the most part in the cell body, with transport
of proteins and polypeptides to the axonal ending by
axoplas-
mic flow.
Thus, the cell body maintains the functional and an-
atomic integrity of the axon; if the axon is cut, the part distal to
the cut degenerates
(wallerian degeneration). Orthograde
transport
occurs along microtubules that run along the length
of the axon and requires two molecular motors, dynein and ki-
nesin (Figure 4–4). Orthograde transport moves from the cell
body toward the axon terminals. It has both fast and slow com-
ponents;
fast axonal transport
occurs at about 400 mm/day,
and
slow axonal transport
occurs at 0.5 to 10 mm/day.
Retro-
grade transport,
which is in the opposite direction (from theCLINICAL BOX 4–1
Demyelinating Diseases
Normal conduction of action potentials relies on the insulat-
ing properties of
myelin.
Thus, defects in myelin can have
major adverse neurological consequences. One example is
multiple sclerosis (MS),
an autoimmune disease that af-
fects over 3 million people worldwide, usually striking be-
tween the ages of 20 and 50 and affecting women about
twice as often as men. The cause of MS appears to include
both genetic and environmental factors. It is most common
among Caucasians living in countries with temperate cli-
mates, including Europe, southern Canada, northern United
States, and southeastern Australia. Environmental triggers
include early exposure to viruses such as Epstein-Barr virus
and those that cause measles, herpes, chicken pox, or influ-
enza. In MS, antibodies and white blood cells in the immune
system attack myelin, causing inflammation and injury to
the sheath and eventually the nerves that it surrounds. Loss
of myelin leads to leakage of K
+
through voltage-gated
channels, hyperpolarization, and failure to conduct action
potentials. Typical physiological deficits range from muscle
weakness, fatigue, diminished coordination, slurred speech,
blurred or hazy vision, bladder dysfunction, and sensory dis-
turbances. Symptoms are often exasperated by increased
body temperature or ambient temperature. Progression of
the disease is quite variable. In the most common form,
transient episodes appear suddenly, last a few weeks or
months, and then gradually disappear. Subsequent epi-
sodes can appear years later, and eventually full recovery
does not occur. Others have a progressive form of the dis-
ease in which there are no periods of remission. Diagnosing
MS is very difficult and generally is delayed until multiple
episodes occur with deficits separated in time and space.
Nerve conduction tests
can detect slowed conduction in
motor and sensory pathways. Cerebral spinal fluid analysis
can detect the presence of
oligoclonal
bands indicative of
an abnormal immune reaction against myelin. The most de-
finitive assessment is
magnetic resonance imaging (MRI)
to visualize multiple scarred (sclerotic) areas in the brain.
Although there is no cure for MS, some drugs (eg,
β
-inter-
feron)
that suppress the immune response reduce the se-
verity and slow the progression of the disease.