PT  - JOURNAL ARTICLE
AU  - R. C. Hogg
AU  - C. Trequattrini
AU  - L. Catacuzzeno
AU  - A. Petris
AU  - F. Franciolini
AU  - D. J. Adams
TI  - Mechanisms of Verapamil Inhibition of Action Potential Firing in Rat Intracardiac Ganglion Neurons
DP  - 1999 Jun 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 1502--1508
VI  - 289
IP  - 3
4099  - http://jpet.aspetjournals.org/content/289/3/1502.short
4100  - http://jpet.aspetjournals.org/content/289/3/1502.full
SO  - J Pharmacol Exp Ther1999 Jun 01; 289
AB  - 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. The American Society for Pharmacology and Experimental Therapeutics