Role of inositol 1,4,5-trisphosphate in the regulation of ventricular Ca^2 + signaling in intact mouse heart

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• 作者：Ariel L. Escobar^a ; Claudia G. Perez^b ; Mariano E. Reyes^a ; Sarah G. Lucero^b ; Dmytro Kornyeyev^a ; Rafael Mejí ; a-Alvarez^c ; Josefina Ramos-Franco^b ; ^{jrfranco@rush.edu}
• 关键词：Inositol 1 ; 4 ; 5-trisphosphate ; Caged InsP3 ; Photolysis ; Calcium ; InsP3R ; RyR
• 刊名：Journal of Molecular and Cellular Cardiology
• 出版年：2012
• 出版时间：December, 2012
• 年：2012
• 卷：53
• 期：6
• 页码：768-779
• 全文大小：3632 K

文摘

Inositol 1,4,5-trisphosphate (InsP₃R)-mediated Ca^2 + signaling is a major pathway regulating multiple cellular functions in excitable and non-excitable cells. Although InsP₃-mediated Ca^2 + signaling has been extensively described, its influence on ventricular myocardium activity has not been addressed in contracting hearts at the whole-organ level. In this work, InsP₃-sensitive intracellular Ca^2 + signals were studied in intact hearts using laser scanning confocal microscopy and pulsed local-field fluorescence microscopy. Intracellular [InsP₃] was rapidly increased by UV flash photolysis of membrane-permeant caged InsP₃. Our results indicate that the basal [Ca^2 +] increased after the flash photolysis of caged InsP₃ without affecting the action potential (AP)-induced Ca^2 + transients. The amplitude of the basal [Ca^2 +] elevation depended on the intracellular [InsP₃] reached after the UV flash. Pretreatment with ryanodine failed to abolish the InsP₃-induced Ca^2 + release (IICR), indicating that this response was not mediated by ryanodine receptors (RyR). Thapsigargin prevented Ca^2 + release from both RyR- and InsP₃R-containing Ca^2 + stores, suggesting that these pools have similar Ca^2 + reuptake mechanisms. These results were reproduced in acutely isolated cells where photorelease of InsP₃ was able to induce changes in endothelial cells but not in AP-induced transients from cardiomyocytes. Taken together, these results suggest that IICR does not directly regulate cardiac excitation-contraction coupling. To our knowledge, this is the first demonstration of IICR in intact hearts. Consequently, our work provides a reference framework of the spatiotemporal attributes of the IICR under physiological conditions.