Molecular aspects of the voltage sensor of ionic channels: structure, kinetics and evolution

Abstract

Electrical signaling constitutes one of the primary means of communication in the nervous system and other excitable tissues with the voltage-gated ion channels being responsible for initiating and propagating electrical impulses. Voltage-gated ion channels are also involved in different mechanisms related to body homeostasis such as intracellular regulation of calcium and hydrogen ion concentrations. Due to those reasons, the physical properties of these channels and its interaction with chemical agents have been extensively studied during the last decades. The voltage-gated ion channels exist in three functional states depending on transmembrane voltage: closed, open or inactivated. The improvement of molecular biology, electrophysiology and crystallography techniques jumped up the ion channel studies to a molecular level. However, structure/functional states studies are scarce in the literature and low disseminated in Brazil. Taking advantage from my experience obtained in the Department of Physiology of University of Wisconsin, we intent to open a new research line in the Departamento de Biofísica of Unifesp, focusing our studies on ion channel structure/function relationship. The research topics associated with this proposal have specific interest on the activity of the voltage sensor of voltage-gated ion channels and comprise: i) the coupling between the voltage sensor and pore of potassium channels; ii) the functional characterization of negative charged residues of the voltage sensor of domain IV to the inactivation of sodium channels and; iii) the co-evolution analysis of voltage-gated proton channels. (AU)