Sex differences in cardiac muscle responsiveness to Ca 2+ and L-type Ca 2+ channel modulation

Abstract

This study investigated sex-related differences in rat papillary muscle force generation in response to altered extracellular [Ca 2+] ([Ca 2+] o, 0.2 to 5.0 mM) and to L-type Ca 2+ channel modulators (nifedipine and Bay K8644). At all [Ca 2+] o examined, contractile force was significantly greater in male than female papillary muscles. The [Ca 2+] o required for 50% maximum force was significantly lower in male [0.34 ± 0.06 mM] than female [0.61 ± 0.10 mM] papillary muscles. Nifedipine decreased contractile force in papillary muscles of both sexes in a concentration-dependent manner, but the extent of the contractile depression was more marked in male papillary muscles at all nifedipine concentrations examined. BayK 8644 produced a concentration-dependent increase in contractile force in male papillary muscles but notably, not in female papillary muscles. These findings show that sex differences in myocardial mechanical function are associated with sex-specific modulation of L-type Ca 2+ channel responsiveness. Thus, the L-type Ca 2+ channel could represent an important cellular locus from which sex-based differences in myocardial excitation–contraction coupling arise.