Sex differences in cardiac muscle responsiveness to Ca2+ and L-type Ca2+ channel modulation.
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.
Curl
Claire L
CL
Department of Physiology, Monash University, Australia. ccurl@unimelb.edu.au
Delbridge
Lea M D
LM
Wendt
Igor R
IR
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000494:pharmacology*; D002120:Calcium Channel Agonists / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D020746:Calcium Channels, L-Type / Q000187:drug effects*; D005260:Female; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium; D010210:Papillary Muscles / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D012727:Sex Characteristics
D002120:Calcium Channel Agonists; D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D002118:Calcium