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NEMATODES 319
energy-independent ion transporters (e.g.
Na /H antiporter, Na /HCO 3 symporter,
HCO 3 /Cl exchanger). Genes that encode
most of these ion transport proteins have been
identified in C. elegans. However, the functions
of only a few have been studied in vitro, and
their expression patterns in nematode tissues
have not been reported. It is not yet known how
many are expressed in the hypodermis or internal
transport tissues.
The crucial importance of regulating inorganic
ion concentrations across nematode cells
is illustrated by the effects of several drugs that
interfere with ion channels. The anthelmintic
actions of ivermectin and other macrocyclic lactones,
for example, are attributed to the ability
of these compounds to open Cl channels associated
with glutamate receptors in the pharynx
(see below). By increasing the permeability of
these cells to Cl , the pharyngeal membrane
becomes hyperpolarized, usually by only a few
mV, but this is sufficient to reduce its responsiveness
to excitatory nerve impulses. This leads
to flaccid paralysis of the pharynx and, eventually,
starvation and loss of ability by the worm to
remain at its site of predilection within the host.
Two other classes of anthelmintics, the imidazothiazoles
and tetrahydropyrimidines, exemplified
by levamisole and pyrantel, respectively,
target cholinergic receptors on somatic muscle
membranes. These receptors are directly coupled
to channels for Na and Ca 2 which, when
opened by these drugs, lead to depolarization
and spastic paralysis of the somatic musculature.
The actions of several other anthelmintics,
such as piperazine and the paraherquamides,
are attributable to their direct or indirect effects
on ion channels associated with nerve and
muscle membranes. Unfortunately, no data are
available on the effects of anthelmintics on electrochemical
gradients maintained across hypodermal
or tubular cells in nematodes, and
information on their effects on anterior regions
of the alimentary tract is only just beginning to
emerge. Thus, although pharmacological experiments
have provided tremendous insights into
ion transport mechanisms in nematode neuromuscular
systems, we have a very limited grasp
of related proteins that maintain ionic gradients
within the pseudocel or across other internal
membranes that regulate the environment
around muscle and nerve cells.
The largest and most accessible structural
barrier separating internal compartments in
the nematode from the environment is the
cuticle–hypodermis complex. Though the cuticle
forms as an extracellular secretion from
the hypodermis, it is possible to separate these
structures by experimental procedures and
study their individual contributions to the transmural
transport of ions and other solutes. The
cuticle is 50–100 m thick in adult A. suum,
but much thinner in other species. Aqueous
pores that traverse the cuticle are negatively
charged, and therefore present an electrostatic
barrier to the transport of large organic
anions. However, due to the large radius of
these pores (15 Å in A. suum) compared to the
size of relevant inorganic anions (Cl , radius
1.2 Å), size has little influence on inorganic
anion transport across the cuticle. This is best
demonstrated by data from electrophysiological
studies that measured electrical potential
and current flux across isolated body wall segments
of A. suum. An electrical potential of
30 mV (muscle-side negative) develops very
rapidly when tissue segments containing living
muscle and hypodermis are placed between
the two half-cells of a diffusion cell system
(Ussing chamber). When muscle and hypodermal
tissues are mechanically scraped from
this preparation, and residual lipid removed
by extraction with chloroform and methanol,
the transmural potential is abolished and there
remains no resistive barrier to the passage of
small inorganic ions, measured as electrical
BIOCHEMISTRY AND CELL BIOLOGY: HELMINTHS