Preferential block of the veratridine-induced, non-inactivating Na+ current by R56865 in single cardiac Purkinje cells.
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.
Verdonck
F
F
Katholieke Universiteit Leuven, Kortrijk, Belgium.
Bielen
F V
FV
Ver Donck
L
L
D000818:Animals; D052160:Benzothiazoles; D006321:Heart / Q000187:drug effects; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects; D009206:Myocardium / Q000166:cytology / Q000378:metabolism; D010880:Piperidines / Q000494:pharmacology*; D011689:Purkinje Cells / Q000187:drug effects / Q000378:metabolism*; D011817:Rabbits; D015222:Sodium Channels / Q000187:drug effects*; D013779:Tetrodotoxin / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology*; D014701:Veratridine / Q000494:pharmacology*
D052160:Benzothiazoles; D010880:Piperidines; D015222:Sodium Channels; D013844:Thiazoles; D013779:Tetrodotoxin; D014701:Veratridine; C054551:R 56865