DESCRIPTION OF MODAL GATING OF THE CARDIAC CALCIUM-RELEASE CHANNEL INPLANAR LIPID-MEMBRANES

Single channel activity of the cardiac ryanodine-sensitive calcium-rel ease channel in planar lipid membranes was studied in order to elucida te the calcium-dependent mechanism of its steady-state behavior. The s ingle channel kinetics, observed with Cs+ as the charge carrier at dif ferent activating (cis) Ca2+ concentrations in the absence of ATP and Mg2+, were similar to earlier reports and were extended by analysis of channel modal behavior. The channel displayed three episodic levels o f open probability defining three gating modes: H (high activity), L ( low activity), and I (no activity). The large difference in open proba bilities between the two active modes resulted from different bursting patterns and different proportions of two distinct channel open state s. I-mode was without openings and can be regarded as the inactivated mode of the channel; L-mode was composed of short and sparse openings; and H-mode openings were longer and grouped into bursts. Modal gating may explain calcium-release channel adaptation (as transient prevalen ce of H-mode after Ca2+ binding) and the inhibitory effects of drugs ( as stabilization of mode I), and it provides a basis for understanding the regulation of calcium release.