The Big Picture

I use both electrophysiology (i.e. cut-open voltage clamp and two-electrode voltage clamp) and x-ray crystallography to elucidate functional and structural mechanism of C-type inactivation in eukaryotic voltage-gated potassium channels, respectively.

Voltage-gated K+ channels open and close in response to the alterations in the cell’s membrane potential. In humans, they are commonly found in repolarizing the membrane potential to resting state after a neural or cardiac action potential. C-type inactivation, a.k.a. “slow inactivation”, plays an essential part in this repolarization step by kinetically regulating K+ conduction. Mechanistically, it involves intracellular and extracellular conformational changes of the channel in or near the selectivity filter to prevent conduction of ions. Using Kv1.2, Shaker and KcsA, I aim to uncover the mechanistic characteristic of C-type inactivation across various K+ channels. I will also use molecular dynamics simulations to study the conformational landscapes between known structures to study intermediate structures.