Open structure of the Ca ²⁺ gating ring in the high-conductance Ca ²⁺-activated K ⁺ channel

High-conductance voltage-and Ca ²⁺-activated K ⁺ channels function in many physiological processes that link cell membrane voltage and intracellular Ca ²⁺ concentration, including neuronal electrical activity, skeletal and smooth muscle contraction, and hair cell tuning. Like other voltage-dependent K ⁺ channels, Ca ²⁺-activated K ⁺ channels open when the cell membrane depolarizes, but in contrast to other voltage-dependent K ⁺ channels, they also open when intracellular Ca ²⁺ concentrations rise. Channel opening by Ca ²⁺ is made possible by a structure called the gating ring, which is located in the cytoplasm. Recent structural studies have defined the Ca ²⁺-free, closed, conformation of the gating ring, but the Ca ²⁺-bound, open, conformation is not yet known. Here we present the Ca ²⁺-bound conformation of the gating ring. This structure shows how one layer of the gating ring, in response to the binding of Ca ²⁺, opens like the petals of a flower. The degree to which it opens explains how Ca ²⁺ binding can open the transmembrane pore. These findings present a molecular basis for Ca ²⁺ activation of K ⁺ channels and suggest new possibilities for targeting the gating ring to treat conditions such as asthma and hypertension.