Transcriptional regulation of intermolecular Ca <sup>2+</sup> signaling in hibernating ground squirrel cardiomyocytes: The myocardin–junctophilin axis
Lei Yang, Rong-Chang Li, Bin Xiang, Yi‐Chen Li, Lipeng Wang, Yun-Bo Guo, Jinghui Liang, Xiaoting Wang, Tingting Hou, Xin Xing, Zeng-Quan Zhou, Haihong Ye, Renqing Feng, Edward G. Lakatta, Zhen Chai, Shi‐Qiang Wang
Abstract
Significance The efficiency of excitation–contraction coupling in heart cells depends partially on the interaction between junctophilin-2 in the sarcoplasmic reticulum and caveolin-3 on T-tubules. Decreased junctophilin-2 has been linked to heart failure. Here, we found that the transcription of junctophilin-2 and caveolin-3 is controlled concurrently by the serum response factor and myocardin. During the entree into hibernation in ground squirrels, the up-regulation of myocardin boosts junctophilin-2/caveolin-3 expression and enhances the efficiency of excitation–contraction coupling. This finding not only reveals an adaptive mechanism underlying the blood-pumping power in hibernation, but also offers a strategy to correct deficient Ca 2+ signaling in heart diseases.