Depression of the Spontaneous Activity by Phorbol Esters in Young Embryonic Chick Cardiomyocytes
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概要
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Effects of phorbol esters, 12-<I>O</I>-tetradecanoyl-phorbol-13-acetate (TPA) and 4-β-phorbol-12, 13-dibutyrate (PDB), that stimulate protein kinase C (PK-C) on the spontaneous action potential and the ionic currents in cultured embryonic chick ventricular cardiomyocytes were examined using whole-cell voltage-clamp and current-clamp modes. Experiments were performed at room temperature (22°C). The firing rate of spontaneous activity was 61.7± 1.6 beats/min (n=12). Phorbol esters (100 nM and 1 μM) caused a negative chronotropic effect, and they inhibited the maximum rate of depolarization and the action potential amplitude. The action potential duration (at 50% repolarization) tended to decrease, and the maximum diastolic potential was unaffected. In whole-cell voltage-clamp experiments, both TPA and PDB inhibited the L-type Ca<SUP>2+</SUP> current and the delayed rectifier K<SUP>+</SUP> current. The fast time constant of the inactivation phase for the Ca<SUP>2+</SUP>2+ current was decreased, but the slow component was unaffected. In addition, PDB (100 nM) enhanced the T-type Ca<SUP>2+</SUP> current, accompanied with an increase in its time constant. In contrast, 4--phorbol-12, 13-didecanoate (PDD), an inactive analogue on PK-C, failed to produce significant changes. These results suggest that the PK-C stimulation induced by phorbol esters might affect the ionic currents and modulate the [Ca]<SUB>i</SUB>, resulting in regulation of the spontaneous activity of embryonic chick heart cells.
- 社団法人 日本薬理学会の論文
- 1995-04-01
著者
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Satoh Hiroyasu
Department Of Chemistry School Of Science Kitasato University
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Satoh Hiroyasu
Department Of Pharmacology Nara Medical University
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