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 limited 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 separate single channels, 9 responded to ADPR by a complete closure, while 14 channels showed no response at all, resulting in a reduction in overall open probability in the presence of ADPR (relative to control channels) by 39.7%. Although the ADPR-responsive and unresponsive single channels showed no differences in their respective open times, current amplitudes or relative occurrences of dwell levels, the bare existence of two types of response to ADPR together with the 50%-limited inhibition of cardiac SR Ca2+ release by ADPR indicates a heterogeneity of RyRCs in cardiac SR, which is likely due to protein(s) that interact(s) with the channel and are present in substoichiometric mole ratios.