HETEROGENEITY OF THE CARDIAC CALCIUM-RELEASE CHANNEL AS ASSESSED BY ITS RESPONSE TO ADP-RIBOSE

ADP-ribose (ADPR) was found to decrease the rate of Ca2+ release from isolated cardiac sarcoplasmic reticulum (SR) vesicles, which was limit ed to a maximum of 46 +/- 8% inhibition and was in accordance with our results obtained with single cardiac ryanodine receptor Ca2+ release channels (RyRC) incorporated into planar lipid bilayers: Out of 23 sep arate single channels, 9 responded to ADPR by a complete closure, whil e 14 channels showed no response at all, resulting in a reduction in o verall open probability in the presence of ADPR (relative to control c hannels) by 39.7%. Although the ADPR-responsive and unresponsive singl e channels showed no differences in their respective open times, curre nt amplitudes or relative occurrences of dwell levels, the bare existe nce of two types of response to ADPR together with the 50%-limited inh ibition of cardiac SR Ca2+ release by ADPR indicates a heterogeneity o f RyRCs in cardiac SR, which is likely due to protein(s) that interact (s) with the channel and are present in substoichiometric mole ratios. (C) 1995 Academic Press, Inc.