Preferential block of the veratridine-induced, non-inactivating Na + current by R56865 in single cardiac Purkinje cells

Abstract

The effect of the cardioprotective agent R56865 on the veratridine (VTD)-modified sodium current was investigated in single rabbit cardiac Purkinje cells and ventricular myocytes. A steady, tetrodotoxin (TTX)-sensitive Na + current (the non-inactivating Na + current) was absent in most cells studied. In the presence of veratridine (15 × 10 −6 M) a non-inactivating Na + current could be elicited at membrane potentials between −80 to +60 mV, with a maximum at about 0 mV. R56865 blocked this current effectively. The concentration for half maximal inhibition of the non-inactivating Na + current was 2 × 10 −7 M. Blockade of this Na + current by R56865 increased with depolarization. R56865 was much more effective in inhibiting the non-inactivating Na + current than in inhibiting time-dependent Na + currents elicited by short depolarizing pulses. The blocking effect of R56865 on the steady state influx of Na + may contribute to cardioprotection in depolarized cells and in cells with modified Na + channels as may occur during ischaemia and reperfusion.