Transcriptional regulation of intermolecular Ca2+ signaling in hibernating ground squirrel cardiomyocytes: The myocardin–junctophilin axis

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 Ca2+ signaling in heart diseases.