Negative inotropic effects of endothelin-1 in mouse cardiomyocytes: evidence of a role for Na+-Ca2+ exchange.
Endothelin-1 (ET-1) is a peptide hormone produced within the myocardium which may modulate myocardial contractility in a paracrine-autocrine fashion. In the majority of species, ET-1 has a direct positive inotropic effect on the myocardium that involves both increased myofilament Ca(2+) sensitivity and increased Ca(2+) transients. Ca(2+) entry through reverse-mode Na(+)-Ca(2+) exchange, involving both indirect effects via elevation of intracellular [Na(+)] and direct activation of the Na(+)-Ca(2+) exchanger, have been suggested to contribute to the increase in Ca(2+) transients. Conversely, mouse cardiomyocytes show an exclusively negative inotropic response to ET-1. Here, Nishimaru and colleagues present novel evidence that the negative inotropic effect of ET-1 in mouse cardiomyocytes involves both a reduction in myofilament Ca(2+) sensitivity and increased Ca(2+) extrusion, via Na(+)-Ca(2+) exchange. Data obtained using the selective Na(+)-Ca(2+) exchange blocker, SEA0400, suggest that a re-assessment of the role of the exchanger in Ca(2+)-handling by mouse cardiomyocytes may be necessary.
James
A F
AF
Department of Physiology and Pharmacology and Bristol Heart Institute Cardiovascular Research Laboratories, School of Medical Sciences, University of Bristol, University Walk, Bristol, UK. a.james@bristol.ac.uk
D000814:Aniline Compounds / Q000494:pharmacology; D000818:Animals; D048430:Cell Shape / Q000187:drug effects*; D019332:Endothelin-1 / Q000494:pharmacology*; D051379:Mice; D009200:Myocardial Contraction / Q000187:drug effects; D032383:Myocytes, Cardiac / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D010647:Phenyl Ethers / Q000494:pharmacology; D019831:Sodium-Calcium Exchanger / Q000037:antagonists & inhibitors / Q000502:physiology
D000814:Aniline Compounds; D019332:Endothelin-1; D010647:Phenyl Ethers; C430918:SEA 0400; D019831:Sodium-Calcium Exchanger