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+-release channels/ryanodine receptors (RyRs). It allows channel activity to decay during sustained increases in the concentration of activating Ca2+. Despite the potential physiological importance of this self-confining process, its molecular mechanism is not well understood. To define the mechanism of adaptation we studied the dynamics of cardiac Ca2+-release channel (RyR) gating using the planar lipid bilayer technique in combination with photolysis of caged Ca2+ (DM-nitrophen). Channels activated by rapid and sustained increases in Ca2+ concentration (from 0.1 to 0.5 micromol/l) displayed three distinct gating modes, manifested as current records with frequent and long openings (H-mode), with rare and short openings (L-mode), and with no openings (I-mode). H-mode channel activity occurred primarily at early times while L- and I-modes predominated at late times after the rapid Ca2+ concentration increase. The decrease in probability of H-mode, mirrored by an increase in the probability of the I-mode, proceeded with a time constant similar to that observed for spontaneous decay in channel activity (i.e., adaptation) in ensemble average records. These results indicate that RyR adaptation transpires by a shift of channel gating from a high open probability mode to low open probability and inactivated modes of the channel.
Institute of Molecular Physiology and Genetics, Slovak Academy of Sciences, 83334 Bratislava, Slovak Republic.
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Zahradníková
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Dura
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S
Györke
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D004285:Dogs; D015640:Ion Channel Gating / Q000502:physiology*; D007700:Kinetics; D008051:Lipid Bilayers / Q000378:metabolism; D008861:Microsomes / Q000737:chemistry; D009206:Myocardium / Q000737:chemistry* / Q000378:metabolism / Q000648:ultrastructure; D010782:Photolysis; D019837:Ryanodine Receptor Calcium Release Channel / Q000502:physiology*; D012519:Sarcoplasmic Reticulum / Q000648:ultrastructure
D008051:Lipid Bilayers; D019837:Ryanodine Receptor Calcium Release Channel; D002118:Calcium