Open structure of the Ca²⁺ gating ring in the high-conductance Ca²⁺-activated K⁺ channel

High-conductance voltage- and Ca²⁺-activated K⁺ channels function in many physiological processes that link cell membrane voltage and intracellular Ca²⁺ concentration, including neuronal electrical activity, skeletal and smooth muscle contraction, and hair cell tuning. Like other voltage-dependent K⁺ channels, Ca²⁺-activated K⁺ channels open when the cell membrane depolarizes, but in contrast to other voltage-dependent K⁺ channels, they also open when intracellular Ca²⁺ concentrations rise. Channel opening by Ca²⁺ is made possible by a structure called the gating ring, which is located in the cytoplasm. Recent structural studies have defined the Ca²⁺-free, closed, conformation of the gating ring, but the Ca²⁺-bound, open, conformation is not yet known. Here we present the Ca²⁺-bound conformation of the gating ring. This structure shows how one layer of the gating ring, in response to the binding of Ca²⁺, opens like the petals of a flower. The degree to which it opens explains how Ca²⁺ binding can open the transmembrane pore. These findings present a molecular basis for Ca²⁺ activation of K⁺ channels and suggest new possibilities for targeting the gating ring to treat conditions such as asthma and hypertension. ©2011

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