PMID: 8971735Dec 1, 1996Paper

Action of tertiary phenylalkylamines on cardiac transient outward current from outside the cell membrane

Naunyn-Schmiedeberg's Archives of Pharmacology
J W Wegener, H Nawrath

Abstract

The effects of the phenylalkylamines verapamil (V), gallopamil (G), and devapamil (D) and their corresponding quaternary derivatives on the transient outward current (Ito) were examined in rat ventricular cardiomyocytes using the whole-cell patch-clamp technique. The question was addressed, whether phenylalkylamines act on Ito from the inside or the outside or from both sides of the cell membrane. To this end, the myocytes were either superfused extracellularly or perfused intracellularly with drug-containing solutions. In addition, the effects of verapamil were investigated at different pH-values. V, G, and D (30 microM each), applied extracellularly, reduced the steady state current of Ito, Ito(150 ms), to 34 +/- 3.3, 33 +/- 6, and 30 +/- 5, respectively (% of control; means +/- SEM). The effects of V (30 microM) on Ito were similar at various external pH-values (reduction of Ito(150 ms) by 69 +/- 6 at pH 6.5, by 66 +/- 4 at pH 7.4, by 68 +/- 8 at pH 8.5, and by 58 +/- 10 at pH 9.5; % of control; means +/- SEM). In contrast, the effect of 4-aminopyridine (300 microM) on Ito was enhanced after alkalinisation: the peak current of Ito was reduced to 49 +/- 5 at pH 7.4 and to 5 +/- 2 at pH 9.2 (% of control; means +/- SEM). V, G,...Continue Reading

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Citations

Feb 22, 2001·Biochemical and Biophysical Research Communications·T P CalmelsA Bril

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