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following exposure to environmentally realistic levels of methylmercury. This obser-
vation was made both in mink and common loons.
In summary, the toxic effects of methylmercury on vertebrates are complex and
wide ranging, and with the present state of knowledge it is not possible to ascribe this
neurotoxicity to one clearly defined mode of action.
16.4 effectS on tHe functIonIng of tHe nerVouS SyStem
Following combination with their sites of action, the main consequent effects of the
neurotoxic compounds described here are upon synaptic transmission or propagation
of action potential. In some cases (e.g., methylmercury and some OPs) there are signs
of physical damage such as demyelination, phagocytosis of neurons, etc. The follow-
ing account will be mainly concerned with effects of the first kind—that is, electro-
physiological effects—which may provide the basis for assays that can monitor the
progression of toxicity from an early stage and thus provide a measure of sublethal
effects caused by differing levels of exposure. Effects on the peripheral nervous sys-
tem and the central nervous system will now be considered separately.
16.4.1 e
f f e c T s
o n
T h e
p
e r i p h e r a l
n
e r v o u s
s
y s T e m
Electrical impulses are passed along nerves as a consequence of the rapid progres-
sion of a depolarization of the axonal membrane. In the resting state, a transmem-
brane potential is maintained on account of the impermeability of the nerve to ions
such as Na
+
and K
+
. Were the membrane freely permeable, these ionic gradients
could not be sustained. Active transport processes maintain ionic gradients in excess
of those that could be achieved purely by passive diffusion. However, when Na
+
channels open in the axonal membrane, a very brief inwardly flowing Na
+
current
causes a transient depolarization. This is rapidly corrected by a subsequent outward
flow of K
+
ions. The Na
+
current is terminated when the pore channel closes, and the
succeeding K
+
current flows briefly until the transmembrane potential returns to its
resting state (Figure 16.1).
The passage of action potentials along a nerve can be recorded by inserting
microelectrodes across the neuronal membrane and using them to record changes in
the transmembrane potential in relation to time. This has been done in a variety of
ways. Microelectrodes can be inserted into nerves of living animals, or into isolated
nerves, or cellular preparations of nerve cells (see Box 16.2). An important refine-
ment of the technique involves “voltage clamping.” This permits the “fixing” of the
transmembrane potential, which restricts the movement of ions across the mem-
brane. Thus, it is possible to measure just the Na
+
current or the K
+
current in control
and in “poisoned” nerves, thereby producing a clearer picture of the mechanism of
action of neurotoxic compounds that affect the conduction of action potentials along
nerves. Measurements of this kind may be just of spontaneous action potentials or of
potentials that are elicited by electrical or chemical stimulation. Chemical stimula-
tion may be accomplished using natural neurotransmitters such as acetylcholine.
The effects of neurotoxic chemicals upon nerve action potential have been mea-
sured both in vertebrates and insects. Of particular interest has been the comparison
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