Saturation characteristics, Ca2+ ions and drug-induced block of cardiac Isi-mediated action potentials

Kohlhardt, M.

doi:10.1007/bf00497671

Cited by 7 publications

(1 citation statement)

References 31 publications

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“…Also for emetine dihydrochloride it could be shown that the negative inotropic effect is abolished by raising extracellular calcium concentration. Both the negative inotropic activity and the reduction of the slow calcium inward current by verapamil and nifedipine could be attenuated by a high extracellular calcium concentration (Kohlhardt, 1983). Lee & Tsien (1983) compared the inhibitory effects of gallopamil, diltiazem and nitrendipine in guinea-pig ventricular myocytes in the presence of 3 mm and 30 /tM Ca, and in each case elevation of the extracellular calcium concentration significantly increased the percentage of unblocked calcium channels.…”

Section: Single Channel Currentmentioning

confidence: 99%

Cardiotoxicity of emetine dihydrochloride by calcium channel blockade in isolated preparations and ventricular myocytes of guinea‐pig hearts

Lemmens‐Gruber¹,

Karkhaneh²,

Studenik³

et al. 1996

British J Pharmacology

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The cardiotoxic effects of emetine dihydrochloride on mechanical and electrical activity were studied in isolated preparations (papillary muscles, sinoatrial and atrioventricular nodes, ventricular myocytes) of the guinea‐pig heart. Force of contraction was measured isometrically, action potentials and maximum rate of rise of the action potential were recorded by means of the intracellular microelectrode technique. Single channel L‐type calcium current (Ba2+ ions as charge carrier) was studied with the patch‐clamp technique in the cell‐attached mode. Emetine dihydrochloride (8–256 μm) reduced force of contraction in papillary muscles and spontaneous activity of sinoatrial and atrioventricular nodes concentration‐dependently; the negative inotropic effect was abolished when the extracellular Ca2+ concentration was increased. Maximum diastolic potential, action potential amplitude, maximum rate of rise of the action potential and the slope of the slow diastolic depolarization were decreased by emetine in sinoatrial as well as atrioventricular nodes, while action potential duration was prolonged in both preparations (1–64 μm). The amplitude of the L‐type calcium single channel current was not altered by emetine dihydrochloride, while average open state probability was decreased concentration‐dependently (10, 30 and 60 μm). The most prominent effect of emetine dihydrochloride on single channel current was an increase of sweeps without activity. At 60 μm, emetine dihydrochloride caused a decrease of the mean open time and an increase of the mean closed time. The number of openings per record and number of bursts per record were reduced. It is concluded that emetine dihydrochloride produces an L‐type calcium channel block which might contribute to its cardiac side effects.

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Section: Single Channel Currentmentioning

confidence: 99%

Cardiotoxicity of emetine dihydrochloride by calcium channel blockade in isolated preparations and ventricular myocytes of guinea‐pig hearts

Lemmens‐Gruber¹,

Karkhaneh²,

Studenik³

et al. 1996

British J Pharmacology

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Competitive interactions between Bay K 8644 and nifedipine in K+ depolarized smooth muscle: a passive role for Ca2+?

Spedding¹

1985

Naunyn-Schmiedeberg's Arch. Pharmacol.

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The kinetics of the interactions between Bay K 8644, a calcium channel activator, and the "calcium-antagonists" nifedipine, verapamil and diltiazem have been investigated. Nifedipine shifted cumulative concentration-response curves for Ca2+ to the right in K+ depolarized taenia preparations from the guinea-pig caecum. The apparent pA2 was 9.3 +/- 0.2 (slope 1.44; 95% confidence limits 0.99-1.88). Bay K 8644 (10-1,000 nmol/l) reduced the inhibitory effects of nifedipine, shifting the Schild plots to the right, without affecting the slope of the nifedipine:Ca2+ interaction. Thus, the interaction between the dihydropyridines was independent of external Ca2+. The parallel shifts of the Schild plots allow a novel interpretation of the "agonist" potency of Bay K 8644 because the compound had an apparent pA2 of 8.8 (slope 0.92) as an "antagonist" of the inhibitory effects of nifedipine. In contrast, Bay K 8644 was a non-competitive antagonist of the inhibitory effects of verapamil and diltiazem on Ca2+-induced contractions. These findings emphasize the differences between the various classes of "calcium-antagonists" and show that Bay K 8644 is a powerful tool discriminating between them.

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[3H]-nitrendipine binding in membranes obtained from hypoxic and reoxygenated heart

Matucci¹,

Bennardini²,

Sciammarella³

et al. 1987

Biochemical Pharmacology

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Saturation characteristics, Ca2+ ions and drug-induced block of cardiac Isi-mediated action potentials

Cited by 7 publications

References 31 publications

Cardiotoxicity of emetine dihydrochloride by calcium channel blockade in isolated preparations and ventricular myocytes of guinea‐pig hearts

Cardiotoxicity of emetine dihydrochloride by calcium channel blockade in isolated preparations and ventricular myocytes of guinea‐pig hearts

Competitive interactions between Bay K 8644 and nifedipine in K+ depolarized smooth muscle: a passive role for Ca2+?

[3H]-nitrendipine binding in membranes obtained from hypoxic and reoxygenated heart

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