FORCE-FREQUENCY RESPONSE IN ISOPROTERENOL-INDUCED HYPERTROPHIED RAT-HEART

Rate-dependent force production was investigated using small trabecula r muscle from control and hypertrophied rat cardiac muscle. Cardiac hy pertrophy was induced by daily subcutaneous injection of isoproterenol (0.3 mg/kg body weight) for 12 days. The force-frequency relationship , for the control rat myocardium, is clearly biphasic. A stepped incre ase in stimulation frequency from 0.1 to 0.5 Hz results in a decrease in contractile force (negative phase). However, at higher stimulation frequency above 0.5 Hz, an increased contractile force is revealed (po sitive phase). Membrane action potential duration (APD(50)) was used t o reflect sarcolemmal Ca2+ influx. The frequency-dependent increase in APD(50) and the ability of nifedipine, a sarcolemmal L-type Ca2+ chan nel blocker, to eliminate the positive-force frequency response, indic ate that sarcolemmal Ca-2+ influx is important for force development a t high stimulation frequency. Relative Ca2+ content of sarcoplasmic re ticulum is estimated from rapid cooling contractures. The parallel cha nge of rapid cooling contractures and twitch force suggests that the s arcoplasmic reticulum Ca2+ content alters with varying frequencies of stimulation. Isoproterenol-induced hypertrophied muscle shows a greate r contractile force, increased nifedipine-sensitive force development and prolonged APD(50) compared to controls. These data suggest a great er availability of intracellular Ca2+ to activate contraction in hyper trophied muscle, possibly by amplified Ca2+ influx via L-type channel.