Dual effects of cyclic ADP-ribose on sarcoplasmic reticulum Ca2+ release and storage in cardiac myocytes isolated from guinea-pig and rat ventricle.

Abstract The actions of cyclic ADP-ribose (cADPR), a regulator of Ca 2+ -induced Ca 2+ release (CICR), were investigated on Ca 2+ release and sarcoplasmic reticulum (SR) Ca 2+ loading in cardiac myocytes at physiological temperature. In guinea-pig ventricular cells, cADPR, applied via patch pipette or from photorelease of its caged derivative, increased contraction amplitude and whole-cell Ca 2+ transients, without affecting SR Ca 2+ load (measured in response to rapid caffeine application). Under voltage-clamp conditions, photorelease of caged cADPR enhanced Ca 2+ transient magnitude without affecting the peak amplitude of L-type Ca 2+ current or its rate of decay, indicative of an increase in CICR gain. In rat permeabilised ventricular myocytes, rapid application of cADPR increased Ca 2+ spark frequency within 30 s, and this effect was maintained over a 10 min exposure. Enhancement of spark frequency was not associated with changes in SR Ca 2+ load at 30 s and 3 min of exposure to cADPR; however, prolonged exposure (10 min) was associated with an increased SR Ca 2+ load (32 ± 7%). The observations are consistent with dual actions of cADPR: a rapid effect on CICR that does not depend on an increased SR Ca 2+ load, and an additional slower effect that is associated with enhanced SR Ca 2+ levels.