Role of voltage-sensitive release mechanism in depression of cardiac contraction in myopathic hamsters.
We investigated excitation-contraction (EC) coupling in isolated ventricular myocytes from prehypertrophic cardiomyopathic (CM) hamster hearts. Conventional and voltage-clamp recordings were made with high-resistance microelectrodes, and cell shortening was measured with a video-edge detector at 37 degrees C. Contractions were depressed in myocytes from CM hearts, whether they were initiated by action potentials or voltage-clamp steps. As in guinea pig and rat, contraction in hamster myocytes could be triggered by a voltage-sensitive release mechanism (VSRM) or Ca(2+)-induced Ca(2+) release (CICR). Selective activation of these mechanisms demonstrated that the defect in EC coupling was primarily caused by a defect in the VSRM. However, activation and inactivation properties of the VSRM were not altered. When the VSRM was inhibited, the remaining contractions induced by CICR exhibited identical bell-shaped contraction voltage relations in normal and CM myocytes. Inward Ca(2+) current was unchanged. Thus a defect in the VSRM component of EC coupling precedes the development of hypertrophy and failure in CM hamster heart.
Howlett
S E
SE
Cardiovascular Research Laboratories, Department of Pharmacology, Dalhousie University, Halifax, Nova Scotia, Canada B3H 4H7.
Xiong
W
W
Mapplebeck
C L
CL
Ferrier
G R
GR
D000818:Animals; D002118:Calcium / Q000378:metabolism / Q000494:pharmacology; D009202:Cardiomyopathies / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D006224:Cricetinae; D004594:Electrophysiology; D008297:Male; D009200:Myocardial Contraction; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D012016:Reference Values; D016276:Ventricular Function
D002118:Calcium