Inhibition of the fast Na+ inward current by the Ca2+ channel blocker tiapamil.
The inhibitory effect of the phenylalkylamine-type Ca2+-entry blocker, tiapamil, on the fast Na+ inward current was investigated in guinea-pig papillary muscles by measuring the maximum upstroke velocity (dV/dt)max of transmembrane action potentials. Tiapamil inhibited (dV/dt)max at concentrations above 10(-6) M, with an IC50 value of 7 X 10(-5) M (1 Hz stimulation frequency, 5.9 mM extracellular K+). Verapamil was less potent in depressing upstroke velocity. Inhibition of the dV/dtmax strongly depended on the frequency at which the muscles were stimulated ("use-dependent" effect). There was no evidence that tiapamil acts in a potential-dependent manner like local anesthetics. The results indicate that the Ca2+-entry blocker tiapamil has additional pharmacological properties, which may contribute to its usefulness in the treatment of ventricular arrhythmias.
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D004558:Electric Stimulation; D006168:Guinea Pigs; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D007473:Ion Channels / Q000187:drug effects*; D008564:Membrane Potentials / Q000187:drug effects; D011189:Potassium Chloride / Q000494:pharmacology; D011437:Propylamines / Q000494:pharmacology*; D013976:Tiapamil Hydrochloride; D014700:Verapamil / Q000494:pharmacology
D002121:Calcium Channel Blockers; D007473:Ion Channels; D011437:Propylamines; D011189:Potassium Chloride; D014700:Verapamil; D013976:Tiapamil Hydrochloride