Potentiation of the contraction following a prolonged depolarization in isolated ferret myocardium

Abstract

The contractile force was studied in ferret papillary muscles during voltage clamp depolarizations, using the single sucrose gap method. Prolongation of a test depolarization within a train produced potentiation of the following contraction. The effects of varied duration and membrane potential of the test depolarization upon the potentiated force of the following beat were studied. We assumed that force of a beat was an index of calcium entry on the previous depolarization. The relationship between the peak contractile force of the following potentiated beat and the systolic membrane potential of the test depolarization revealed an equilibrium around -18 mV. This was manifest after 100 ms of no effect. Positive potentials caused potentiation of force of the following beat; negative potentials caused suppression of force of the following beat. Calcium entry, if carried by an electrogenic exchange mechanism, would be revealed as a membrane current developing after 100 ms. Membrane current at these times was always outward. When the duration of the test depolarization was prolonged, outward current prior to repolarisation progressively increased. When the duration of the test depolarization was held constant, outward current was varied by variation in membrane potential. Force of the following beat was proportional to the test clamp membrane potential. The potentiation of the contraction following a prolonged depolarization was abolished by substituting 75% of the sodium in the perfusion medium with lithium. These results are compatible with the hypothesis that potentiation of force following a prolonged depolarization is derived from calcium entry into myocardial cells by reversed sodium-calcium exchange.

The beat-to-beat decay of cardiac contractility from highly potentiated levels is bi-exponential

“…During studies of isolated ferret papillary muscle in which we have applied voltage clamp pulses (Arlock and Wohlfart, 1990;Arlock et al, 1991aArlock et al, , b, 1998Noble et al, 1993), we observed that the beat-to-beat decay of isometric force following potentiation was faster than that reported in the intact heart (ter Keurs et al, 1990) or in experiments using standard field stimulation. In the present study, we studied decay of potentiation over a wider range of contractility than that previously explored, and found that the beat-to-beat decay of contractility is not mono-exponential, but bi-exponential (Fig.…”

“…There is a residual constant ''c'' which, in the analysis of the present study, is the asymptotic value to which we have normalised the data, i.e., 1.0. ''c'' is known to be a function of action potential duration (Drake-Holland et al, 1983) or voltage clamp duration (Arlock et al, 1998). The decay of post-extrasystolic potentiation is now an accepted method for the analysis of the recirculated fraction of calcium ions from beat-to-beat in heart muscle (Rice et al, 2000;Hata et al, 1997;Lee et al, 2000;Shimizu et al, 2000).…”