Research Interests
The nervous system has long been recognized as one of
the most susceptible organ systems to insult from toxic environmental
contaminants due to its limited capacity to repair tissue damage. Unlike
other tissues such as liver, kidney or skin, for which cellular repair
occurs readily, toxicity to the nervous system is generally irreversible.
During the last few years, interest has focused on the study of neurotoxicology.
This is due to the heightened awareness of society to the potential for
neurotoxicity following disastrous or potentially disastrous episodes
of contamination seen with agents such as methylmercury in Japan and Iraq,
polychlorinated and polybrominated biphenyls in Taiwan and here in the
U.S.A., and insecticides such as mirex and kepone. Historically, most
neurotoxicology studies have focused on pathological descriptions of the
lesions observed clinically in affected individuals. Few mechanistic studies
at the cellular level have been undertaken, so the toxic mechanisms of
action of these agents remain largely unknown.
My research interest is the study of effects of chemicals
on the nervous system, particularly those chemicals which act directly
on the synapse. My primary research interest is in the cellular mechanism
of action of chemicals which disrupt Ca2+-dependent processes at the membrane
and intracelluarly. A variety of techniques including electrophysiological
recordings of ion channel activity (patch-voltage clamp) and synaptic
transmission (intracellular and extracellular microelectrode recording
techniques), neurochemical analysis of synaptic function and fluorescent
microscopy and digital imaging of intracellular ion concentrations using
fluorescent probes such as Fura-2. Toxicological research interests are
presently focused on the effects of heavy metals such as methylmercury,
many of which exert potent toxic actions at chemical synapses, and on
the mechanism of delayed neurotoxicity caused by certain sulfur-containing
agents. A second area of interest in my laboratory is the pharmacology
and physiology of neurotransmitter release in the peripheral and central
nervous system, especially identifying the molecular entities involved
in Ca2+-dependent neurosecretion.
Selected Publications
Search all publications in the NCBI Journal Database
Pardo NE, Hajela RK, Atchison WD. Acetylcholine release at neuromuscular junctions of adult Tottering mice is controlled by N- (Cav2.2) and R- (Cav2.3), but not L-type (Cav1.2) Ca2+ channels. J. Pharmacol. Exp. Ther. 2006 Sep 18; [Epub ahead of print]
Edwards, J.R., Marty, M.S., Atchison, W.D. Comparative sensitivity of rat cerebellar neurons to dysregulation of divalent cation homeostasis and cytotoxicity caused by methylmercury. Toxicol. Appl. Pharmacol. 208: 222-32, 2005.
Yuan, Y., Atchison, W.D. Methylmercury induces a spontaneous, transient slow inward chloride current in Purkinje cells of rat cerebellar slices. J. Pharmacol. Exp. Ther. 313: 751-64, 2005.
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William
D. Atchison