A less flexible BK channel opens more easily

Abstract

BK potassium channels regulate spike width and firing rate. A BK point mutation in humans enhances channel activity, leading to epilepsy. In this issue of Neuron, Yang and colleagues use this mutation to demonstrate that channel opening is determined by the flexibility of a region that contains a Ca(2+)-binding site.

Figure 1

Schematic diagram of the cytoplasmic C-terminal domain of one of the four subunits of a BK channel. Regions important for Ca²⁺ gating, starting from the N terminus are: the S6 linker (blue rectangle), RCK1, AC region, RCK2, and the putative Ca²⁺ binding sites; D367 and the “Ca²⁺ bowl”. The D369G mutation, blue circle, in the AC region of RCK1 couples (circular arrow) only to the D367 pathway and enhances channel activity by reducing protein flexibility.