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)