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.
Zahradníková
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Department of Physiology and Biophysics, University of Texas Medical Branch, Galveston 77555.
Palade
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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