Differential antagonism of the negative inotropic effect of gentamicin by calcium ions, Bay K 8644 and isoprenaline in canine ventricular muscle: Comparison with cobalt ions

H. Hashimoto, T. Yanagisawa, N. Taira

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

1. Gentamicin (10-4-10-2 M) and Co2+ (10-4-10-2 M) produced a decrease in developed tension of canine isolated ventricular muscles leading to near abolition at 10-2 M. Their negative inotropic effects developed rapidly and wore off shortly after wash-out. 2. The concentration-negative inotropic effect curves for gentamicin were shifted to the right in a parallel manner by increasing external Ca2+, or by the presence of Bay K 8644 (10-7-10-5 M) or isoprenaline (10-7-10-5 M). IC50 values for gentamicin increased about 3-fold with about a 6 fold increase in external Ca2+. The Schild plot yielded a pA2 of 2.29 for Ca2+ and its slope was -1.17 (r = -0.79). 3. The concentration-negative inotropic effect curves for Co2+ were shifted to the right in a parallel manner by increasing external Ca2+, or by the presence of isoprenaline (10-7-10-5 M). IC50 values for Co2+ increased about 5-fold with about a 6-fold increase in external Ca2+. The Schild plot gave a pA2 value of 2.60 for Ca2+ and its slope was -1.11 (r = -0.86). 4. The concentration-positive inotropic effect curves for Ca2+, which were computer-fitted to a logistic equation, gave 2.88 x 10-3 M for EC50. This value was very close to the K(Ca) calculated from pA2 values for Ca2+ based on antagonism between gentamicin or Co2+ and Ca2+ (5.13 x 10-3 and 2.51 x 10-3 M). 5. It is concluded that like Co2+, gentamicin molecules compete with Ca2+ for the same binding sites presumably located at the outer orifice of Ca-channels in the cardiac sarcolemma.

Original languageEnglish
Pages (from-to)906-912
Number of pages7
JournalBritish Journal of Pharmacology
Volume96
Issue number4
DOIs
Publication statusPublished - 1989

ASJC Scopus subject areas

  • Pharmacology

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