Sex differences in cardiac muscle responsiveness to Ca2+ and L-type Ca2+ channel modulation

• Published in: European journal of pharmacology Vol. 586; no. 1-3; pp. 288 - 292
• Main Authors: CURL, Claire L, DELBRIDGE, Lea M. D, WENDT, Igor R
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier 31-05-2008
• Subjects: 3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester - pharmacology; Animals; Biological and medical sciences; Calcium - pharmacology; Calcium Channel Agonists - pharmacology; Calcium Channel Blockers - pharmacology; Calcium Channels, L-Type - drug effects; Female; Male; Medical sciences; Myocardial Contraction - drug effects; Myocardium; Papillary Muscles - drug effects; Pharmacology. Drug treatments; Rats; Rats, Wistar; Sex Characteristics; Heart; Calcium; Papillary muscle; Contractility; Sex; Gender; Inorganic element; Myocardial contractility; Myocardium; Muscle; Circulatory system; L-type calcium channel; Cardiovascular sex differences; Calcium flux
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/j.ejphar.2008.02.053

This study investigated sex-related differences in rat papillary muscle force generation in response to altered extracellular [Ca2+] ([Ca2+](o), 0.2 to 5.0 mM) and to L-type Ca2+ channel modulators (nifedipine and Bay K8644). At all [Ca2+]o examined, contractile force was significantly greater in male than female papillary muscles. The [Ca2+]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 Ca2+ channel responsiveness. Thus, the L-type Ca2+ channel could represent an important cellular locus from which sex-based differences in myocardial excitation-contraction coupling arise.