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(1-8). 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(9). 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.