
KV10.1チャネルの細胞内ドメインの変異により、通常は検出されない大きな導電状態が現れ、チャネルのゲーティングメカニズムの詳細が明らかになった。


coremsg

The KCNH family of potassium channels serves relevant physiological functions in both excitable and non-excitable cells, reflected in the massive consequences of mutations or pharmacological manipulation of their function. This group of channels shares structural homology with other voltage-gated K+ channels, but the mechanisms of gating in this family show significant differences with respect to the canonical electromechanical coupling in these molecules. In particular, the large intracellular domains of KCNH channels play a crucial role in gating that is still only partly understood. Using KCNH1 (KV10.1) as a model, we have characterized the behavior of a series of modified channels that could not be explained by the current models. With electrophysiological and biochemical methods combined with mathematical modeling, we show that the uncovering of an open state can explain the behavior of the mutants. This open state, which is not detectable in wild-type channels, appears to lack the rapid flicker block of the conventional open state. Because it is accessed from deep closed states, it elucidates intermediate gating events well ahead of channel opening in the wild type. This allowed us to study gating steps prior to opening, which, for example, explain the mechanism of gating inhibition by Ca2+-Calmodulin and generate a model that describes the characteristic features of KCNH channels gating.

### Competing Interest Statement

The authors have declared no competing interest.

Revealing a hidden conducting state by manipulating the intracellular domains in KV10.1 exposes the coupling between two gating mechanisms

kv10-1-チャネルの細胞内ドメインを操作することで隠された導電状態を明らかにし-2つのゲーティングメカニズムの連関を明らかにする


KV10.1 チャネルの細胞内ドメインを操作することで隠された導電状態を明らかにし、2つのゲーティングメカニズムの連関を明らかにする
