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

The effects of verapamil and related phenylalkylamines on neuronal excitabi lity were investigated in isolated neurons of rat intracardiac ganglia usin g whole-cell perforated patch-clamp recording. Verapamil (greater than or e qual to 10 mu M) inhibits tonic firing observed in response to depolarizing current pulses at 22 degrees C. The inhibition of discharge activity is no t due to block of voltage-dependent Ca2+ channels because firing is not aff ected by 100 mu M 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 degrees C. Verapamil does not antagonize the acetylcholine-induced inhibition of the muscarine-sensi tive K+ current (M-current) in rat intracardiac neurons. Verapamil inhibits the delayed outwardly rectifying K+ current with an IC50 value of 11 mu M, Which is approximately 7-fold more potent than its inhibition of high volt age-activated Ca2+ channel currents. These data suggest that verapamil inhi bits tonic firing in rat intracardiac neurons primarily via inhibition of d elayed outwardly rectifying K+ current. Verapamil inhibition of action pote ntial firing in intracardiac neurons may contribute, in part, to verapamil- induced tachycardia.