Vol. 289, Issue 3, 1502-1508, June 1999

Mechanisms of Verapamil Inhibition of Action Potential Firing in Rat Intracardiac Ganglion Neurons¹

R. C. Hogg, C. Trequattrini, L. Catacuzzeno, A. Petris, F. Franciolini and D. J. Adams

Department of Physiology and Pharmacology, University of Queensland, Brisbane, Queensland, Australia (R.C.H., D.J.A.); and Dipartmento Biologia Cellulare e Molecolare, Universita' di Perugia, Perugia, Italy (C.T., L.C., A.P., F.F.)

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.