Possible mechanisms underlying differences in force production between normal and cardiomyopathic hamster atria.
The rate of recovery of force after a long rest interval is lower than normal in left atria from 80- to 85-day-old cardiomyopathic (CM) golden Syrian hamsters. To determine whether this difference was due to a reduced amount of Ca2+ available for release with each beat, we manipulated the amount of Ca2+ entering excised atria using the Ca2+ agonist BAY K 8644 and the antagonist nifedipine. We also simulated altered Ca2+ influx in a recent model of cardiac excitation-contraction coupling (V. J. A. Schouten, J. K. Van Deen, P. de Tombe, and A. A. Verveen Biophys. J. 51: 13-26, 1987) by varying the parameter representing Ca2+ influx and observing the effect on the force it predicted. Steady-state force of normal and CM atria was recorded in response to 1-Hz stimulation and recovery of steady-state force was monitored after a 600-s rest interval. Ca2+ fluxes were manipulated by raising external Ca2+ or by the presence and absence of drug. The recovery of force after a 600-s rest interval was digitized and fitted with an exponential function, and the time constant and steady-state force to which the muscle recovered after the pause were compared. Inclusion of the Ca2+ agonist BAY K 8644 (0.25 or 2.0 microM) made the response of CM atria similar to that of normal, while inclusion of the Ca2+ antagonist nifedipine (0.8 microM) made the response of normal atria similar to that of the CM. Similarly, decreasing the simulated Ca2+ influx in the model produced all of the differences observed between normal and CM muscle.(ABSTRACT TRUNCATED AT 250 WORDS)
Bobet
J
J
Department of Pharmacology, University of Alberta, Edmonton, Canada.
Howlett
S E
SE
Gordon
T
T
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 / Q000502:physiology; D009202:Cardiomyopathies / Q000503:physiopathology*; D006224:Cricetinae; D004305:Dose-Response Relationship, Drug; D006321:Heart / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology*; D006325:Heart Atria; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D008647:Mesocricetus; D009200:Myocardial Contraction / Q000187:drug effects; D009543:Nifedipine / Q000494:pharmacology; D012016:Reference Values
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D009543:Nifedipine; D002118:Calcium