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Bepridil (CERM-1978) blockade of action potentials in cultured rat aortic smooth muscle cells

Authors
Journal
European Journal of Pharmacology
0014-2999
Publisher
Elsevier
Publication Date
Volume
71
Issue
1
Identifiers
DOI: 10.1016/0014-2999(81)90382-4
Keywords
  • Calcium Antagonistic Agent
  • Arterial Muscle
  • Electrophysiology
  • Blood Vessels
  • Bepridil
  • Vascular Smooth Muscle
  • Cell Cultures
Disciplines
  • Biology

Abstract

Abstract Reaggregate cultures (primary) were prepared from enzyme-dispersed vascular smooth muscle (VSM) cells from rat aortas. The cultures were incubated for 7–10 days, and then studied by the intracellular microelectrode technique. The cells were electrically quiescent (mean resting potential of −47 mV), and extracellular electrical stimulation usually did not elicit a membrane response. Addition of 10 mM tetraethylammonium rapid induced excitability, allowing the VSM cells to fire Ca 2+-dependent action potentials in response to electrical stimulation. The electrical responses often had two components, an intial spike and a later plateau-like component. The action potential spikes had a mean amplitude of 22 mV but occasionally were overshooting; the plateaus had a mean duration (at 50% repolarization) of 3.8 sec. A new anti-anginal agent,, bepridil (10 −8–10 −5 M), depressed the amplitude and duration of the plateau and blocked the spike component of the action potential in a dose-dependent fashion without affecting the resting potential. This finding is consistent with the view that bepridil acts as a Ca 2+-antagonistic agent to prevent the generation of the action potentials, and this action can be explain its anti-anginal properties.

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