title: Mechanisms of verapamil inhibition of action potential firing in rat intracardiac ganglion neurons.
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 microM) inhibits tonic firing observed in response to depolarizing current pulses at 22 degrees C. The inhibition of discharge activity is not due to block of voltage-dependent Ca2+ channels because firing is not affected by 100 microM 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-sensitive K+ current (M-current) in rat intracardiac neurons. Verapamil inhibits the delayed outwardly rectifying K+ current with an IC50 value of 11 microM, 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.
authors.affiliation: Department of Physiology and Pharmacology, University of Queensland, Brisbane, Queensland, Australia.
authors.forename: R C
authors.initials: RC
authors.lastname: Hogg
authors.forename: C
authors.initials: C
authors.lastname: Trequattrini
authors.forename: L
authors.initials: L
authors.lastname: Catacuzzeno
authors.forename: A
authors.initials: A
authors.lastname: Petris
authors.forename: F
authors.initials: F
authors.lastname: Franciolini
authors.forename: D J
authors.initials: DJ
authors.lastname: Adams
mesh_terms: D015761:4-Aminopyridine / Q000494:pharmacology; D000109:Acetylcholine / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects*; D000818:Animals; D000831:Animals, Newborn; D001030:Apamin / Q000494:pharmacology; D002478:Cells, Cultured; D018999:Charybdotoxin / Q000494:pharmacology; D004558:Electric Stimulation; D005726:Ganglia, Parasympathetic / Q000502:physiology*; D006321:Heart / Q000294:innervation*; D008564:Membrane Potentials / Q000187:drug effects; D009116:Muscarine / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D018408:Patch-Clamp Techniques; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000502:physiology; D051381:Rats; D019789:Tetraethylammonium / Q000494:pharmacology; D014700:Verapamil / Q000494:pharmacology*
chemical_list: D026902:Potassium Channel Blockers; D015221:Potassium Channels; D018999:Charybdotoxin; D001030:Apamin; D019789:Tetraethylammonium; D009116:Muscarine; D015761:4-Aminopyridine; D014700:Verapamil; D000109:Acetylcholine