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

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 I Na (labelled here I Na1 ). With steps to −40 mV or less negative values, a slowly decaying component (tentatively labelled here I Na2 ) appeared, which peaked at −30 to −20 mV and decayed slowly and incompletely during the 500 ms steps. The I Na2 was present also during steps to −10 mV, but then the transient outward current ( I to ) appeared. When the holding potential ( V h ) was decreased to −60 to −50 mV, I Na2 disappeared even if a small I Na1 might still be present. Tetrodotoxin (30 μ m ), lignocaine (100 μ m ) and cadmium (0.2 m m ; but not manganese, 1 m m ) blocked I Na2 . During fast depolarizing ramps, the rapid inactivation of I Na1 was followed by a negative slope region. During repolarizing ramps, a region of positive slope was present, whereas I Na1 was absent. At less negative values of V h , the amplitude of the negative and positive slopes became gradually smaller. Gradually faster ramps increased the magnitude of the negative slope, and tetrodotoxin (30 μ m ) reduced or abolished it. Thus, Purkinje cells have a slowly decaying inward current owing to Na + entry ( I Na2 ) that is different in several ways from the fast I Na1 and that appears important for the duration of the plateau.