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

• Published in: European journal of pharmacology Vol. 203; no. 3; p. 371
• Main Authors: Verdonck, F, Bielen, F V, Ver Donck, L
• Format: Journal Article
• Language: English
• Published: Netherlands 22.10.1991
• Subjects: Animals; Benzothiazoles; Heart - drug effects; In Vitro Techniques; Membrane Potentials - drug effects; Myocardium - cytology; Myocardium - metabolism; Piperidines - pharmacology; Purkinje Cells - drug effects; Purkinje Cells - metabolism; Rabbits; Sodium Channels - drug effects; Tetrodotoxin - pharmacology; Thiazoles - pharmacology; Veratridine - pharmacology
• ISSN: 0014-2999
• DOI: 10.1016/0014-2999(91)90893-U

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 x 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 x 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 ischemia and reperfusion.