INHIBITION OF THE FAST NA+ INWARD CURRENT BY THE CA-2+ CHANNEL BLOCKER TIAPAMIL

  • 1 January 1986
    • journal article
    • research article
    • Vol. 8  (6) , 1101-1106
Abstract
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 .times. 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.