Force-frequency relation in frog-ventricle is dependent on the direction of sodium/calcium exchange in diastole

Force of contraction increases with stimulus-frequency in mammalian and amphibian hearts under control conditions. Here, we have analysed the mechanism of the force-frequency relation (FFR) in frog-ventricle.

Circular strips of frog-ventricle were subjected to field-stimulation with frequencies in the range 0.03-0.2 Hz and force recorded on a chart-recorder. In another protocol, varying rest-periods were imposed while the preparation beat steadily at 0.2 Hz and the effect of rest on post-rest beat amplitude was noted.

Under control conditions, a positive FFR and a rest-induced decay of contraction amplitude (RID) were seen in the frequency range 0.03-0.2 Hz. With cadmium, nifedipine, nickel (40 micromol L(-1)), ryanodine and adrenaline (all drugs at 10 micromol L(-1) concentration, except nickel), the positive FFR and RID seen under control conditions persisted. When the bathing solution contained ouabain (10 micromol L(-1)) or low external sodium (40 mmol L(-1)), or high external calcium (5 mmol L(-1)), the FFR turned negative in the frequency range stated above and there were rest-induced potentiations (RIP).

When the conditions favour a net leak of calcium in diastole from intracellular stores via the calcium-extrusive mode of sodium-calcium exchanger (NCX), FFR is positive. An increase in frequency lessens the diastolic interval and therefore the diastolic calcium leak, thereby augmenting force. On the other hand, interventions which favour the calcium-acquisitive mode of NCX during diastole, changed the pattern of RID to RIP and converted FFR from positive to negative. With net diastolic calcium uptake, there is better store-filling and therefore higher force at lower frequencies.