Increase in the slow inward current by intracellularly applied nifedipine and nicardipine in single ventricular cells of the guinea-pig heart

T. Iijima, T. Yanagisawa, N. Taira

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

It has long been discussed why dihydropyridine calcium antagonists are less cardioactive than other calcium antagonists at doses equally effective on vascular smooth muscle [5, 12]. Recently, it has been reported that dihydropyridine calcium antagonists, unlike other calcium antagonists, inhibit adenosine 3′,5′-cyclic monophosphate phosphodiesterase in various tissue preparations [2, 8, 10]. It has also been reported that intracellularly applied adenosine 3′,5′-cyclic monophosphate increases the slow inward current in heart cells [1, 11, 13]. Therefore, present experiments were carried out to elucidate the effects of intracellularly applied calcium antagonists on the slow inward current of single ventricular cells with the patchclamp, 'whole-cell recording', technique [3]. Nifedipine, nicardipine and isobutylmethylxanthine, when applied intracellularly using the patch-clamp microelectrode, increased the plateau and the duration of action potentials of single ventricular heart cells of the guinea-pig. The augmentation of the action potential was abolished by superfusing the cell with nifedipine. D600 and diltiazem when applied either intra- or extra-cellularly decreased the plateau and the duration of the action potential. Under voltage clamp conditions, intracellularly applied nifedipine, nicardipine and isobutylmethylxanthine increased the slow inward current, whereas D600 and diltiazem decreased the current. The holding current and the current at the end of 200-ms clamp pulses were not modified. Thus, dihydropyridine calcium antagonists probably increase the slow inward current from the inside of the cell and attenuate the calcium entry blocking activities in heart cells. This must partly be a reason why dihydropyridine calcium antagonists are less cardioactive than D600 and diltiazem at doses equally effective on vascular smooth muscle.

Original languageEnglish
Pages (from-to)1173-1177
Number of pages5
JournalJournal of Molecular and Cellular Cardiology
Volume16
Issue number12
DOIs
Publication statusPublished - 1984 Dec

Keywords

  • Adenosine 3′,5′-cyclic monophosphate phosphodiesterase
  • Dihydropyridine calcium antagonist
  • Slow inward current

ASJC Scopus subject areas

  • Molecular Biology
  • Cardiology and Cardiovascular Medicine

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