Theoretical and simulation studies on voltage-gated sodium channels.

Yang Li,Haipeng Gong

doi:10.1007/s13238-015-0152-6

Abstract

Voltage-gated sodium (Nav) channels are indispensable membrane elements for the generation and propagation of electric signals in excitable cells. The successes in the crystallographic studies on prokaryotic Nav channels in recent years greatly promote the mechanistic investigation of these proteins and their eukaryotic counterparts. In this paper, we mainly review the progress in computational studies, especially the simulation studies, on these proteins in the past years.

Highlights

As one of the fundamental elements in the membrane of excitable cells, voltage-gated sodium (Nav) channels are critical in the generation and propagation of electrical signals in both nerves and muscles (Hille, 2001), and have become therapeutic targets for many neurological disorders, including epilepsy, migraine, neurodegenerative diseases and neuropathic pain (Clare et al, 2000; Dib-Hajj et al, 2010; Mantegazza et al, 2010)
Many voltage-gated ion channels (VGICs) superfamily members, the voltagegated cation channels (VGCCs) that control the transport of Na+, K+ and Ca2+ ions, adopt similar structural topologies and mechanisms (Hille, 2001; Catterall et al, 2005)
We want to mention two famous biophysical models which have been generally accepted because of their agreement with enormous experimental observations: the HodgkinHuxley model and the knock-on model. The former perfectly explains the relationship between VGCCs and the electrical signaling in excitable cells (Hodgkin and Huxley, 1952) while the latter describes the mechanism of ion permeation in these channels (Hodgkin and Keynes, 1955)

Summary

Introduction

As one of the fundamental elements in the membrane of excitable cells, voltage-gated sodium (Nav) channels are critical in the generation and propagation of electrical signals in both nerves and muscles (Hille, 2001), and have become therapeutic targets for many neurological disorders, including epilepsy, migraine, neurodegenerative diseases and neuropathic pain (Clare et al, 2000; Dib-Hajj et al, 2010; Mantegazza et al, 2010). Many VGIC superfamily members, the voltagegated cation channels (VGCCs) that control the transport of Na+, K+ and Ca2+ ions (named as Nav, Kv and Cav channels respectively), adopt similar structural topologies and mechanisms (Hille, 2001; Catterall et al, 2005).

Results

Conclusion