Voltage-gated potassium (Kv) channels open when the membrane is depolarized and close when hyperpolarized. This exquisite ability to gate in response to changes in membrane voltage underlies a number of pivotal functions of the body, including excitability of nerve and muscle cells, regulation of cell volume and secretion of hormones. A fundamental question is: how does voltage control gating? Our strategy to address this question is depicted in the following schematic:
We have applied this strategy to the prototypical Shaker potassium channel and, more recently, to the hERG potassium channel. Our results demonstrated that:
Proposed a new mechanism for voltage gating
Despite the major breakthroughs in the structural biology of Kv channels, and numerous structure-function studies, the fundamental question of how S4 moves during depolarization and how its movement is coupled to channel opening remains controversial. We are now using biochemical and structural approaches on the Shaker channel as well as the more intriguing hERG potassium channel to address these outstanding questions.