| Summary: | Following the discovery that changes in membrane conductance were responsible for the electrical activity of neurons and that these changes were produced by voltage-dependent changes in ionic permeability, numerous researchers have turned to electrophysiological and optical tools to dissect the mechanisms of the voltage-gated channels that produce changes in membrane ionic permeability. An additional goal has been to use light or other electromagnetic waves for the measurement of endogenous electrical activity and for the external stimulation of electrical activity. I used electrophysiology in combination with structure-function studies and site-directed fluorometry to better understand the voltage-sensing mechanisms of the Shaker and Kv3.1 voltage-gated potassium channels. These studies suggested that the voltage sensing component of these channels undergoes both a vertical translation and a rotation, and that an extracellular component of the channel acts as a modulator of channel activity. I also used these techniques to study and improve the voltage-sensitive fluorescent response of ArcLight, a popular genetically encoded voltage indicator. In addition, I helped discover and characterize the voltage sensitivity indocyanine green, a fluorescent dye with infrared excitation and approval for human use. Finally, I was a collaborator in an attempt to use millimeter waves to induce electrical activity; this attempt provided novel evidence that the mechanism of activity of millimeter waves on cell excitability is thermal in nature.
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