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In the past few years, the scientific community has witnessed
significant progress in the study of ion channels. Technological
advancement in biophysics, molecular biology, and immunology has
been greatly ac celerated, making it possible to conduct
experiments which were deemed very difficult if not impossible in
the past. For example, patch-clamp techniques can now be used to
measure ionic currents generated by almost every type of cell,
thereby allowing us to analyze whole-cell and single channel
events. It is now possible to incorporate purified ion channel
components into lipid bilayers to reconstitute an "excitable
membrane." Gene cloning and monoclonal antibody techniques provide
us with new approaches to the study of the molecular structure of
ion channels. A variety of chemicals have now been found to
interact with ion channels. One of the classical examples is
represented by tetrodotoxin, a puffer fish poison, which was shown
in the early 1960s to block the voltage-activated sodium channel in
a highly specific and potent manner.
'Further establishes the reputation of the series...an invaluable
resource.' -Trends in Pharmacological Sciences, from a review of
Volume 3 Volume 4 explores such emergent topics as:
three-dimensional conceptions of ion channel proteins based on the
available structural and functional data; the structure,
pharmacology, and regulation of the GABAA receptors; and the
Ca2+-dependent K+ channels in adrenal chromatic cell membranes.
'Further establishes the reputation of the series...an invaluable
resource.' -Trends in Pharmacological Sciences, from a review of
Volume 3 Volume 4 explores such emergent topics as:
three-dimensional conceptions of ion channel proteins based on the
available structural and functional data; the structure,
pharmacology, and regulation of the GABAA receptors; and the
Ca2+-dependent K+ channels in adrenal chromatic cell membranes.
In the past few years, the scientific community has witnessed
significant progress in the study of ion channels. Technological
advancement in biophysics, molecular biology, and immunology has
been greatly ac celerated, making it possible to conduct
experiments which were deemed very difficult if not impossible in
the past. For example, patch-clamp techniques can now be used to
measure ionic currents generated by almost every type of cell,
thereby allowing us to analyze whole-cell and single channel
events. It is now possible to incorporate purified ion channel
components into lipid bilayers to reconstitute an "excitable
membrane." Gene cloning and monoclonal antibody techniques provide
us with new approaches to the study of the molecular structure of
ion channels. A variety of chemicals have now been found to
interact with ion channels. One of the classical examples is
represented by tetrodotoxin, a puffer fish poison, which was shown
in the early 1960s to block the voltage-activated sodium channel in
a highly specific and potent manner.
A wealth of information has been accumulated about the function of
ion channels of excitable cells since the extensive and pioneering
voltage clamp studies by Hodgkin, Huxley, and Katz 36 years ago.
The study of ion chan nels has now reached a stage at which a
quantum jump in progress is antici pated. There are many good
reasons for this. Patch clamp techniques origi nally developed by
Neher and Sakmann 12 years ago have made it possible to study the
function of ion channels in a variety of cells. Membrane ionic
currents can now be recorded practically from many types of cells
using the whole-cell patch clamp technique. The opening and closing
of individual ion channels can be analyzed using the single-channel
patch clamp method. Techniques have also been developed to
incorporate purified ion channels into lipid bilayers to
reconstitute an "excitable membrane. " Advanced tech niques
developed in molecular biology, genetics, and immunology, such as
gene cloning and the use of monoclonal antibodies, are now being
applied to the study of ion channels. A variety of drugs have now
been found or are suspected to interact with ion channels to exert
therapeutic effects. In addition to the classical exam ples, as
represented by local anesthetics, many other drugs, including cal
cium antagonists, psychoactive drugs, cardiac drugs, and
anticonvulsants, shown to alter ion channel function. For certain
pesticides such as have been pyrethroids and DDT, sodium channels
are clearly the major target site.
Intoxication of humans and animals has become increasingly
important in recent years as has contamination of the environment
by a variety of chemicals. In order to develop effective means by
which such intoxication and contamination can be properly handled,
it is imperative to know how these environmental agents act in
humans and animals. Despite studies conducted by various
investigators, the mechanisms of action of these environmental
agents have not been fully elucidated. Insecticides are by no means
an exception in terms of the seriousness of the problem and of the
urgency of the need for such information. In order to complete a
picture of the effects of any particular insecticide, it is of
utmost importance that its actions at various levels ranging from
those of molecules to whole animals be analyzed and synthesized. To
understand the toxicological action on animals or humans, it is not
sufficient to know the action at each level only. The actions at
various levels must be integrated to construct a picture of the
toxic effect on the intact organism. However, in spite of the large
body of information that has been accumulated during the past few
decades, little or no attempt has been made to integrate
experimental data obtained at the molecular, cellular, organ, and
animal levels together in order to define the whole picture of
insecticidal action.
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