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(Neurophysiology; Ion Channels, characterization and modulation by neurotransmitters)

Associate Professor
Ph.D.: State University of New York at Stony Brook
Postdoctoral: Case Western Reserve University

Ion channels form the basis for the action potential, the language by which neurons communicate. A goal of neuroscience in general and this lab in particular is to understand how ion channels function to regulate the generation of action potentials. Sympathetic neurons isolated from rat or frog are used as the model system. These neurons are desirable because they are easy to study, have a large variety of ion channels and have a rich background information. The patch clamp technique is used in the whole- cell and cell attached configuration to study the currents generated by ion channels. One focus is the examination of calcium current under control conditions and during inhibition by neurotransmitters. The inhibition is mediated by direct binding of G protein ßg subunits with the calcium channel. Our recent single channel recordings have demonstrated that the calcium channel is not completely inhibited with the G protein ßg subunit bound. Instead the channel opens briefly in the ßg bound state to a state that has been called the reluctant open state (the channel is reluctant to open when ßg is attached). We are currently testing the hypothesis that an action potential can induce the channel to open reluctantly. A second focus is on the effect that Ca2+ has on the neuronal N-type calcium channel. We have evidence that Ca2+ binding alters N-channel confirmation, which affects inactivation properties, the affinity of the channel for blockers and the kinetics of channel gating. One goal is to determine if all the different effects of Ca2+ can be ascribed to a single binding site on the channel or if multiple sites are involved. These sites provide potential targets for modulation of channel function by toxins, physiological ions and disease.

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A PubMed listing of research publications for Keith S. Elmslie, Ph.D.

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