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

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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 and 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. The absence of sodium in these experiments allows examination of membrane currents without contamination of either sodium-calcium exchange currents or sodium currents. In our experiments, both current fluctuations and ITI appear to be explainable by a single mechanism, namely the activation of a non-selective cation channel by intracellular calcium. Our experiments show that once activated by calcium, this channel allows sodium, potassium and calcium ions to pass through it. We conclude that under conditions of calcium overload, the appearance of ITI (whether as a macroscopic membrane current or as fluctuations in membrane current) will depend on the spatial and temporal synchrony of spontaneous fluctuations in intracellular calcium. The possibility that ITI may be activated during the normal cardiac action potential and the consequences of such activation is discussed.