Modal gating transitions in cardiac ryanodine receptors during increases of Ca2+ concentration produced by photolysis of caged Ca2+

Channel adaptation is a basic property of the sarcoplasmic reticulum Ca2+-r elease channels/ryanodine receptors (RyRs). It allows channel activity to d ecay during sustained increases in the concentration of activating Ca2+. De spite the potential physiological importance of this self-confining process , its molecular mechanism is not well understood. To define the mechanism o f adaptation we studied the dynamics of cardiac Ca2+-release channel (RyR) gating using the planar lipid bilayer technique in combination with photoly sis of caged Ca2+ (DM-nitrophen). Channels activated by rapid and sustained increases in Ca2+ concentration (from 0.1 to 0.5 mu mol/l) displayed three distinct gating modes, manifested as current records with frequent and lon g openings (H-mode), with rare and short openings (L-mode), and with no ope nings (I-mode). II-mode channel activity occurred primarily at early times while L- and I-modes predominated at late times after the rapid Ca2+ concen tration increase. The decrease in probability of H-mode, mirrored by an inc rease in the probability of the I-mode, proceeded with a time constant simi lar to that observed for spontaneous decay in channel activity (i.e., adapt ation) in ensemble average records. These results indicate that RyR adaptat ion transpires by a shift of channel gating from a high open probability mo de to low open probability and inactivated modes of the channel.