ACTION-POTENTIAL DURATION AND FORCE-FREQUENCY-RELATIONSHIP IN ISOLATED RABBIT, GUINEA-PIG AND RAT CARDIAC-MUSCLE

The effect of action potential duration and elevated cytosolic sodium concentration on the force-frequency relationship in isolated rabbit, guinea pig and rat papillary muscle preparations was studied. Shorteni ng of action potential duration in guinea pig and rabbit from 150-200 ms to values characteristic of rat (20-40 ms), using the K-(ATP) chann el activator levkromakalim (15 mu mol . l(-1)), markedly reduced the f orce of contraction and converted the positive force-frequency relatio nship into negative one at longer pacing cycle lengths. This conversio n was greatly enhanced in the presence of acetylstrophanthidin (0.2-1 mu mol . l(-1)), an inhibitor of the Na-K pump. Acetylstrophanthidin ( 1 mu mol . l(-1)) alone, however, had no effect on the force-frequency relationship. Prolongation of action potential duration in rat with i nhibitors of cardiac K channels (4-aminopyridine [10 mmol . l(-1)] plu s tetraethylammonium [2 mmol . l(-1)] increased the force of contracti on and abolished the negative force-frequency relationship observed in rat at longer pacing-cycle lengths. It is concluded that both action potential duration and cytosolic sodium concentration are major determ inants of the force-frequency relationship in mammalian myocardium.