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Ben Spiller

Structural Biology of Voltage Gated Ion Channels

Ben Spiller, Pharmacology

Voltage gated ion channels open or close in response to changes in membrane potential. They were the first channels studied; they are responsible for the electrical impulses of nerve cells; they are the channels that multicellular organisms use for signal transduction along neurons, and for initiation of cellular events such as neurosecretion or muscle contraction. They are responsible for a large fraction of cardiac arrhythmias and as such are a major site for drug intervention. They also represent a major target for pain medication, which currently —due to a lack of isoform-specific drugs — is only exploited for local pain relief.

The general features of selectivity, voltage gating, and inactivation in ion channels have been worked out using electrophysiological and molecular biological methods, and much has been inferred from structural studies of potassium channels. My lab is focused on understanding the molecular features of sodium channels, to create a precise, stereo-chemical understanding of selectivity, gating, and inactivation. Toward this end we are working on structure determination of a voltage gated sodium channel by x-ray crystallography. Beyond the structure of the channel itself, we will focus on localization and regulation of sodium channels.

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