5 - Voltage-Gated Ion Channels

Summary

Biochemical studies have cloned, isolated and sequenced the Na+ and other ion channels in their related protein family; cryo-electronmicroscopic structural determinations have characterised details of their structure. Biophysical measurements of intramembrane charge movement provided electrical signatures clarifying the dynamics and mechanisms of the channel conformational responses to membrane voltage change. Such charge movements were demonstrated, studied and quantified in a wide range of ion-channel species and cell types. Finally, radioactive tracer flux experiments examined the basis for their ion selectivity and permeation. Together these detailed characterisations separated and clarified the mechanisms for ion channel gating and channel permeability to specific ions. They identified voltage-sensing modules and how each domain contributed to the ion-specific pore module within each domain of the four-domain structure making up the ion-channel protein. These studies thus together provide a continuing clarification of the molecular basis through which ion channels mediate excitability in biological membranes.