Bacterial voltage-gated sodium channels (BacNa(V)s) from the soil, sea, and salt lakes enlighten molecular mechanisms of electrical signaling and pharmacology in the brain and heart

Abstract

Voltage-gated sodium channels (Na(V)s) provide the initial electrical signal that drives action potential generation in many excitable cells of the brain, heart, and nervous system. For more than 60years, functional studies of Na(V)s have occupied a central place in physiological and biophysical investigation of the molecular basis of excitability. Recently, structural studies of members of a large family of bacterial voltage-gated sodium channels (BacNa(V)s) prevalent in soil, marine, and salt lake environments that bear many of the core features of eukaryotic Na(V)s have reframed ideas for voltage-gated channel function, ion selectivity, and pharmacology. Here, we analyze the recent advances, unanswered questions, and potential of BacNa(V)s as templates for drug development efforts.

Keywords: channel gating; channel pharmacology; ion permeation; structural biology; voltage-gated sodium channel.