A slowly inactivating sodium current (INa2) in the plateau range in canine cardiac Purkinje single cells

Abstract

The action potential of Purkinje fibres is markedly shortened by tetrodotoxin, suggesting the possibility that a slowly inactivating sodium current might flow during the plateau. The aim of the present experiments was to investigate, in canine cardiac Purkinje single cells by means of a whole cell patch clamp technique, whether a sodium current slowly inactivates at less negative potentials and (if so) some of its distinctive characteristics. The results showed that a 500 ms depolarizing step from a holding potential of -90 mV to -50 mV induced the fast inward current INa (labelled here INa1). With steps to -40 mV or less negative values, a slowly decaying component (tentatively labelled here INa2) appeared, which peaked at -30 to -20 mV and decayed slowly and incompletely during the 500 ms steps. The INa2 was present also during steps to -10 mV, but then the transient outward current (Ito) appeared. When the holding potential (Vh) was decreased to -60 to -50 mV, INa2 disappeared even if a small INa1 might still be present. Tetrodotoxin (30 μm), lignocaine (100 μm) and cadmium (0.2 mm; but not manganese, 1 mm) blocked INa2. During fast depolarizing ramps, the rapid inactivation of INa1 was followed by a negative slope region. During repolarizing ramps, a region of positive slope was present, whereas INa1 was absent. At less negative values of Vh, the amplitude of the negative and positive slopes became gradually smaller. Gradually faster ramps increased the magnitude of the negative slope, and tetrodotoxin (30 μm) reduced or abolished it. Thus, Purkinje cells have a slowly decaying inward current owing to Na+ entry (INa2) that is different in several ways from the fast INa1 and that appears important for the duration of the plateau. © 2007 The Authors.