Title

Mechanisms of verapamil inhibition of action potential firing in rat intracardiac ganglion neurons

RIS ID

106113

Publication Details

Hogg, R. C., Trequattrini, C., Catacuzzeno, L., Petris, A., Franciolini, F. & Adams, D. J. (1999). Mechanisms of verapamil inhibition of action potential firing in rat intracardiac ganglion neurons. Journal of Pharmacology and Experimental Therapeutics, 289 (3), 1502-1508.

Abstract

The effects of verapamil and related phenylalkylamines on neuronal excitability were investigated in isolated neurons of rat intracardiac ganglia using whole-cell perforated patch-clamp recording. Verapamil (≥10 μM) inhibits tonic firing observed in response to depolarizing current pulses at 22°C. The inhibition of discharge activity is not due to block of voltage-dependent Ca2+ channels because firing is not affected by 100 μM Cd2+. The K+ channel inhibitors charybdotoxin (100 nM), 4-aminopyridine (0.5 mM), apamin (30-100 nM), and tetraethylammonium ions (1 mM) also have no effect on firing behavior at 22°C. Verapamil does not antagonize the acetylcholine-induced inhibition of the muscarine-sensitive K+ current (M- current) in rat intracardiac neurons. Verapamil inhibits the delayed outwardly rectifying K+ current with an IC50 value of 11 μM, which is approximately 7-fold more potent than its inhibition of high voltage- activated Ca2+ channel currents. These data suggest that verapamil inhibits tonic firing in rat intracardiac neurons primarily via inhibition of delayed outwardly rectifying K+ current. Verapamil inhibition of action potential firing in intracardiac neurons may contribute, in part, to verapamil-induced tachycardia.

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