RT Journal Article
SR Electronic
T1 Mechanisms of Verapamil Inhibition of Action Potential Firing in Rat Intracardiac Ganglion Neurons
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 1502
OP 1508
VO 289
IS 3
A1 R. C. Hogg
A1 C. Trequattrini
A1 L. Catacuzzeno
A1 A. Petris
A1 F. Franciolini
A1 D. J. Adams
YR 1999
UL http://jpet.aspetjournals.org/content/289/3/1502.abstract
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