First report of coupled gating between RyR2 channels. Dog cardiac microsomes reconstituted in bilayers. (A and B) Ca²⁺ current (flowing from a trans chamber compartment—the SR-luminal side of the channels—with ∼50 mM free [Ca²⁺], to a cis compartment with physiological cytosolic [Ca²⁺]) through an individual channel, with an all-points current histogram in B, consistent with a single channel current of 4 pA. (C and D), Currents of 8 pA and histogram suggest a pair of coupled channels. (E and F) Currents and histogram consistent with a trio of fully coupled channels. Note the absence in D and F of any peak for individual openings, and in the 12-pA peak in F a skew, with a “tail” toward lower values that suggests partial closings. Figure minimally modified from Fig. 2 of Marx et al. (2001), reproduced by courtesy of Andrew Marks. Fig. 1 is reprinted with permission from Circulation Research.