The arrhythmogenic current ITI in the absence of electrogenic sodium-calcium exchange in sheep cardiac Purkinje fibres

Abstract

Sheep cardiac Purkinje fibres were voltage clamped with a two-microelectrode technique. Under conditions that are known to elevate intracellular calcium (0 mM-external potassium), membrane currents were examined. In the above conditions, a brief depolarizing pulse leads to an oscillatory inward current (ITI) which peaks at about 300 ms after the repolarization. An after-contraction is also observed, the peak of which occurs about 80 ms after the peak of ITI. This result is in accord with the results of Kass, Lederer, Tsien & Weingart (1978a). We replaced external sodium with an isotonic CaCl2 solution to remove the sodium-calcium exchange mechanism as a possible current carrier for ITI. In the steady state under these conditions an oscillatory membrane current and after-contraction are seen following repolarization. This current was identified as ITI on the basis of its temporal relation to both the repolarization step and the after-contraction. In isotonic CaCl2, ITI has a reversal potential of -37 mV. Because of this fact ITI cannot be explained by an electrogenic sodium-calcium exchange mechanism alone. The reversal potential suggests that ITI arises from a channel which is permeable to both potassium and calcium. Fluctuations of membrane current and of tension were recorded in the steady state at different holding potentials. Power spectral analysis showed that the current fluctuations were at a minimum at a holding potential of -37 mV. Tension fluctuations were, however, relatively constant over the range of membrane potentials examined (-17 to -70 mV). The peak power of the current fluctuations occurred at about 1.5 Hz (at a holding potential of -70 mV). This peak shifted towards higher frequencies with increasing depolarization. A similar shift in frequency was observed for the tension fluctuations. Cross-correlations between membrane current and tension were calculated for various steady membrane potentials. This analysis shows that the current fluctuations are associated with the tension fluctuations, each with a principal period of about 0.5 s. This analysis also shows that at potentials more negative than the reversal potential of ITI, increasing tension is associated with increasing inward current and that the tension fluctuations follow current fluctuations by about 70 ms. At potentials positive to the reversal potential of ITI, increasing tension was associated with increasing outward current. This analysis therefore indicates that the fluctuations in membrane current reverse at a potential similar to the reversal potential of ITI.(ABSTRACT TRUNCATED AT 400 WORDS)