Comparative effects of a new calcium channel antagonist, mepirodipine, on rabbit spontaneously beating sino-atrial node cells

Satoh, Hiroyuki; Hashimoto, Keitaro

doi:10.1016/0014-2999(91)90193-t

Cited by 8 publications

(2 citation statements)

References 23 publications

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“…It is suggested that Ica , T contributes to the early phase during diastole, and Ica, L contributes to the last phase (30,32,33). The Ica , L generates the depolarization of the last part of the pacemaker potential because a dihydropyridine Ca 2+ antagonist prohibited only the last part of the pacemaker potential of SA nodal cells (34)(35)(36). However, the IC,, T current makes a minor contribution to the pacemaker potential since the inhibitors of Ica, T current did not produce any effects on the initial phase of the pacemaker potential (31,37).…”

Section: Discussionmentioning

confidence: 99%

Depression of the Spontaneous Activity by Phorbol Esters in Young Embryonic Chick Cardiomyocytes

Satoh

1995

Japanese Journal of Pharmacology

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ABSTRACT-Effects of phorbol esters, 12-O-tetradecanoyl-phorbol-13-acetate (TPA) and 4-13-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 (22C). The firing rate of spontaneous activity was 61.7± 1.6 beats/min (n=12). Phorbol esters (100 nM and 1 uM) 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 21 current and the delayed rectifier K+ current. The fast time constant of the inactivation phase for the Ca2+ current was decreased, but the slow component was unaffected. In addition, PDB (100 nM) enhanced the T-type Ca 21 current, accompanied with an increase in its time constant. In contrast, 4-a-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];, resulting in regulation of the spontaneous activity of embryonic chick heart cells.

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Section: Discussionmentioning

confidence: 99%

Depression of the Spontaneous Activity by Phorbol Esters in Young Embryonic Chick Cardiomyocytes

Satoh

1995

Japanese Journal of Pharmacology

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“…In contrast, verapamil slightly increased APD in guinea-pig papillary muscle [154]. The APD increase by verapamil was also seen in spontaneously beating rabbit SA nodal cells together with the reduction of V max and APA [155]. The effects of verapamil in nodal tissues included an increase in CL, maximal diastolic potential (MDP) and APD but a reduction in both V max and APA on rabbit SA node tissue [156].…”

Section: Phenylalkylaminesmentioning

confidence: 93%

Class IV Antiarrhythmic Agents: New Compounds Using an Old Strategy

Szentandrássy

Nagy²,

Hegyi³

et al. 2014

CPD

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Cardiac arrhythmias are a major cause of morbidity and mortality in the industrialized world. Among their treatment regimens one can find the calcium channel antagonists (CCAs), the class IV agents. In the cardiovascular system Land T-type calcium channels are found on vascular smooth muscle cells and cardiac myocytes with well defined physiological roles. Inhibition of calcium channels by CCAs has widely been used in clinical practice for several decades. Cardiovascular disorders are one of the many fields of medicine in which CCAs are used for various reasons and conditions. The three main indications of them are hypertension, angina and various cardiac arrhythmias. The most important classes of CCAs are dihydropyridines, phenylalkylamines and benzothiazepines but some newer compounds do not fall into any of these major classes. Dihydropyridines are not used in the antiarrhythmic therapy but are good vasodilators and antianginal agents. In contrast, phenylalkylamines and benzothiazepines exert cardiac actions in vivo and therefore these are one choice of antiarrhythmic drugs. This review focuses on phenylalkylamines, benzothiazepines and on new drugs with potential antiarrhythmic action in the heart as well as the mechanisms how calcium channels antagonism can lead to an antiarrhythmic action.

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Electrophysiological actions of adenosine and aminophylline in spontaneously beating and voltage-clamped rabbit sino-atrial node preparations

Satoh

1993

Naunyn-Schmiedeberg's Arch Pharmacol

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Effects of adenosine (30 to 200 mumol/l) on the spontaneous action potentials and the membrane currents in rabbit sino-atrial node (SA) preparations were examined. Adenosine (30 mumol/l) lengthened the action potential duration and the cycle length. At 100 mumol/l, adenosine also hyperpolarized the maximum diastolic potential. However, the action potential amplitude and the maximum rate of depolarization Vmax) were unaffected. In the presence of adenosine (200 mumol/l), addition of aminophylline (an antagonist) (23-46 mumol/l) shortened the cycle length and depolarized the maximum diastolic potential to the contrary. Aminophylline did not antagonize the prolongation of the action potential. Aminophylline (46 mumol/l) alone decreased the cycle length and the maximum diastolic potential, but did not affect the action potential amplitude, the action potential duration and the Vmax. In the presence of aminophylline (46 mumol/l), addition of adenosine (200 mumol/l) increased the cycle length and the action potential duration, and decreased Vmax. In voltage-clamp experiments, adenosine greatly shifted the background current in the outward direction. Holding potential was -40 mV. Adenosine reduced a slow inward and a time-dependent outward current, in a concentration-dependent manner. Adenosine did not affect the time constant of inactivation phase and the voltages of the half-maximum activation and inactivation for the slow inward current. The activation curve for the outward current was also unaffected. A hyperpolarization-activated inward current was decreased. In the presence of aminophylline (46 mumol/l), adenosine (200 mumol/l) decreased the slow inward current, the time-dependent outward current and the hyperpolarization-activated inward current.(ABSTRACT TRUNCATED AT 250 WORDS)

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Comparative effects of a new calcium channel antagonist, mepirodipine, on rabbit spontaneously beating sino-atrial node cells

Cited by 8 publications

References 23 publications

Depression of the Spontaneous Activity by Phorbol Esters in Young Embryonic Chick Cardiomyocytes

Depression of the Spontaneous Activity by Phorbol Esters in Young Embryonic Chick Cardiomyocytes

Class IV Antiarrhythmic Agents: New Compounds Using an Old Strategy

Electrophysiological actions of adenosine and aminophylline in spontaneously beating and voltage-clamped rabbit sino-atrial node preparations

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