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Masafumi Yano, Takeshi Yamamoto, Abnormal sarcoplasmic reticulum Ca2+ release in heart failure, Cardiovascular Research, Volume 45, Issue 4, March 2000, Pages 1070–1071, https://doi.org/10.1016/S0008-6363(99)00413-7
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We thank Drs. Diaz, Trafford, O’Neill and Eisner for their comments on our paper. We have shown in our article that the Ca2+ release function of cardiac ryanodine receptor (RyR) was indeed altered in heart failure induced by chronic rapid ventricular pacing [1]. Responding to our article, Diaz et al. raised a question as to the idea that the expression or the properties of the RyR are involved in changes of contractility observed in cardiac hypertrophy or failure. They showed that caffeine increased the open probability of the RyR and also increased the magnitude of both the systolic Ca2+ transient and the contraction. However, they also mentioned that this potentiation was completely transient because of the mechanism by which intracellular Ca2+ homeostasis is maintained toward a steady state, i.e. extrusion of Ca2+ via Na-Ca exchange→decrease in SR Ca content.
Indeed, there is a controversy as to the change in the peak value of Ca2+ transient in heart failure. Using the same model of pacing-induced heart failure, Perreault et al. [2] demonstrated that there was no difference in the peak value of Ca2+ transient between normal and heart failure. In contrast, Yao et al. [3] showed a significant reduction of peak Ca2+ transient between normal and heart failure. However, in both studies, the duration of Ca2+ transient was significantly prolonged. The delayed fall of descending portion of Ca2+ transient might be caused by the decrease in the expression and/or activity of the SR Ca2+-ATPase (SERCA II) [4]. The decreased acceleration of Ca2+ transient (prolongation of time to peak Ca2+ transient observed in the above-mentioned two studies [2,3]) may be due mainly to the altered Ca2+ release function of the RyR because no other protein or receptor can induce faster Ca2+ release than the RyR. As proposed by Gomez et al. [5], the altered E-C coupling due to a decrease in the functional coupling between DHP receptor and the RyR might modulate Ca2+ release function of RyR in addition to the alteration of channel property of the RyR per se. The most important new aspect of our study is that although there was no significant difference in the magnitude of Ca2+ release, the rate of rapid Ca2+ release from the RyR was indeed decreased in heart failure, probably leading to a decrease in the acceleration rate of Ca2+ transient.
