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

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 rapidly induced excitability, allowing the VSM cells to fire Ca2+-dependent action potentials in response to electrical stimulation. The electrical responses often had two components, an initial 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 Ca2+-antagonistic agent to prevent the generation of the action potentials, and this action can explain its antianginal properties.