Procaine effects on single sarcoplasmic reticulum Ca2+ release channels.
The effects of the Ca(2+)-induced Ca2+ release blocker procaine on individual sarcoplasmic reticulum Ca2+ release channels have been examined in planar lipid bilayers. Procaine did not reduce the single channel conductance nor appreciably shorten the mean open times of the channel; rather, it increased the longest closed time. These results indicated that procaine interacted selectively with a closed state of the channel rather than with an open state. Gating of the sarcoplasmic reticulum Ca2+ release channel was described by a modified scheme of Ashley and Williams (1990. J. Gen. Physiol. 95:981-1005), including an additional long-lived closed state. Computer simulations determined that procaine was more likely to interact with this long-lived Ca(2+)-bound closed state of the channel rather than with other states of the channel. Simulations with the same model were also able to reproduce a prominent Ca(2+)-sensitive transition between "random" and "bursting" forms of gating of the channel, variations of which may account for "gearshift" behavior reported in studies with this and other single channels.
Department of Physiology and Biophysics, University of Texas Medical Branch, Galveston 77555.
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Zahradníková
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D000818:Animals; D001665:Binding Sites; D055592:Biophysical Phenomena; D001703:Biophysics; D015220:Calcium Channels / Q000187:drug effects* / Q000378:metabolism; D004285:Dogs; D006321:Heart / Q000187:drug effects; D066298:In Vitro Techniques; D015640:Ion Channel Gating / Q000187:drug effects; D007700:Kinetics; D008051:Lipid Bilayers; D008954:Models, Biological; D009124:Muscle Proteins / Q000187:drug effects* / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism; D011343:Procaine / Q000494:pharmacology*; D019837:Ryanodine Receptor Calcium Release Channel; D012519:Sarcoplasmic Reticulum / Q000187:drug effects* / Q000378:metabolism
D015220:Calcium Channels; D008051:Lipid Bilayers; D009124:Muscle Proteins; D019837:Ryanodine Receptor Calcium Release Channel; D011343:Procaine