Mechanisms of verapamil inhibition of action potential firing in rat intracardiac ganglion neurons.
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.
Hogg
R C
RC
Department of Physiology and Pharmacology, University of Queensland, Brisbane, Queensland, Australia.
Trequattrini
C
C
Catacuzzeno
L
L
Petris
A
A
Franciolini
F
F
Adams
D J
DJ
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*
D026902:Potassium Channel Blockers; D015221:Potassium Channels; D018999:Charybdotoxin; D001030:Apamin; D019789:Tetraethylammonium; D009116:Muscarine; D015761:4-Aminopyridine; D014700:Verapamil; D000109:Acetylcholine