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

被引:65
作者
Cui, Y [1 ]
Galione, A [1 ]
Terrar, DA [1 ]
机构
[1] Univ Oxford, Dept Pharmacol, Oxford OX1 3QT, England
基金
英国惠康基金;
关键词
excitation-contraction coupling; ryanodine receptor; sarcoplasmic reticulum;
D O I
10.1042/0264-6021:3420269
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Actions of photoreleased cADP-ribose (cADPR), a novel regulator of calcium-induced calcium release (CICR) from ryanodine-sensitive stores, were investigated in cardiac myocytes. Photoreleased cADPR caused an increase in the magnitude of whole-cell calcium transients studied in mammalian cardiac ventricular myocytes (both guinea-pig and rat) using confocal microscopy). Approx. 15 a was required following photorelease of cADPR for the development of its maximal effect. Photoreleased cADPR also increased the frequency of calcium 'sparks', which are thought to be elementary events which make up the whole-cell calcium transient, and were studied in rat myocytes, but had little or no effect on spark characteristics (amplitude, rise time, decay time and distance to half amplitude). The potentiating effects of photoreleased 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 the actions of photoreleased cADPR on whole-cell calcium transients in mammalian cells. The observations are consistent with the effects of cADPR in enhancing 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 transients. The slow time-course for development of the full effect on whole-cell calcium transients might be taken to indicate that the influence of cADPR on CICR may involve complex molecular interactions rather than a simple direct action of cADPR on the ryanodine-receptor channels.
引用
收藏
页码:269 / 273
页数:5
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