Effects of photoreleased cADP-ribose on calcium transients and calcium sparks in myocytes isolated from guinea-pig and rat ventricle

Actions of photoreleased cADP-ribose (cADPR), a novel regulator of calcium- induced calcium release (CICR) from ryanodine-sensitive stores, were invest igated in cardiac myocytes. Photoreleased cADPR caused an increase in the m agnitude of whole-cell calcium transients studied in mammalian cardiac vent ricular myocytes (both guinea-pig and rat) using confocal microscopy). Appr ox. 15 a was required following photorelease of cADPR for the development o f its maximal effect. Photoreleased cADPR also increased the frequency of c alcium 'sparks', which are thought to be elementary events which make up th e whole-cell calcium transient, and were studied in rat myocytes, but had l ittle or no effect on spark characteristics (amplitude, rise time, decay ti me and distance to half amplitude). The potentiating effects of photoreleas ed cADPR on both whole-cell transients and the frequency of calcium sparks were prevented by cytosolic application of the antagonist 8-amino-cADPR (5 mu M). These experiments, therefore, provide the first evidence in any cell type for an effect of cADPR on calcium sparks, and are the first to show t he actions of photoreleased cADPR on whole-cell calcium transients in mamma lian cells. The observations are consistent with the effects of cADPR in en hancing the calcium sensitivity of CICR from the sarcoplasmic reticulum in cardiac ventricular myocytes, leading to an increase in the probability of occurrence of calcium sparks and to an increase in whole-cell calcium trans ients. The slow time-course for development of the full effect on whole-cel l calcium transients might be taken to indicate that the influence of cADPR on CICR may involve complex molecular interactions rather than a simple di rect action of cADPR on the ryanodine-receptor channels.