Chronic functional suppression of Orai1 using a dominant-negative mutant elevated [Ca2+]i transients and Ca2+ spark amplitudes in female, but not male, adult mouse ventricular cardiomyocytes.
Chronic functional suppression of Orai1 abrogates sex differences in cardiomyocyte excitation-contraction coupling, revealing a novel mechanistic contribution of Orai1 to sexual dimorphism in cardiac function.
The physiological role of the Orai1 channel, a store-operated Ca²⁺ channel (SOC) in adult ventricular cardiomyocytes, remains incompletely defined. Here, we report that Orai1 may contribute to excitation–contraction coupling (ECC) in a sex-specific manner. Using a mouse model with cardiac-specific expression of a dominant-negative human Orai1R91W mutant (C-dnO1), we found elevated Ca²⁺i transients and Ca²⁺ spark amplitudes in female C-dnO1 mice in comparison with littermate wild-type (WT) controls, but not in male mice. The Orai1 protein expression, cellular distribution, and store-operated Ca²⁺ entry (SOCE) activity were similar in WT males and females and equally diminished in both sexes with C-dnO1 expression. These findings reveal that chronic functional suppression of Orai1 abrogates sex differences in cardiomyocyte ECC, uncovering a novel mechanistic contribution of Orai1 to sexual dimorphism in cardiac function.
Bartoli et al. (Thu,) conducted a other in Orai1 channel function in ventricular cardiomyocytes. Cardiac-specific expression of a dominant-negative human Orai1R91W mutant (C-dnO1) vs. Littermate wild-type (WT) controls was evaluated on [Ca2+]i transients and Ca2+ spark amplitudes. Chronic functional suppression of Orai1 using a dominant-negative mutant elevated [Ca2+]i transients and Ca2+ spark amplitudes in female, but not male, adult mouse ventricular cardiomyocytes.