4-aminopyridine activates potassium currents by activation of a muscarinic receptor in feline atrial myocytes.
1. The effects of 4-aminopyridine (4-AP) on action potentials, macroscopic membrane currents and single-channel recording from cardiac left atrial myocytes of the adult cat were studied using the whole-cell and cell-attached configurations of the patch-clamp technique. 2. 4-AP (1 mM) produced a hyperpolarization of the resting membrane potential and a shortening of action potential duration. Under voltage-clamp conditions, we have found that 4-AP increased a background current and a delayed rectifier outward current. These effects were antagonized by atropine. In addition, both effects seemed to be mediated through a pertussis toxin-sensitive G protein. 3. The background current induced by 4-AP displayed properties that are highly similar to those of the inwardly rectifying potassium current activated by acetylcholine (IK(ACh)). The time-dependent potassium current activated by 4-AP has kinetic and pharmacological properties different from those of the delayed rectifier potassium current previously identified in cardiac myocytes. 4. The activation of the delayed rectifier-like potassium current could be explained by the activation of a novel muscarinic receptor subtype in which acetylcholine acts as the antagonist. Another possibility is that 4-AP activates IK(ACh) in a time- and voltage-dependent manner.
Navarro-Polanco
R A
RA
Centro Universitario de Investigaciones Biomédicas, Universidad de Colima, México.
Sánchez-Chapula
J A
JA
D015761:4-Aminopyridine / Q000494:pharmacology*; D000109:Acetylcholine / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology; D001285:Atropine / Q000494:pharmacology; D001711:Biotransformation / Q000187:drug effects; D002415:Cats; D004232:Diuretics / Q000494:pharmacology; D004594:Electrophysiology; D006325:Heart Atria / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D066298:In Vitro Techniques; D007190:Indapamide / Q000494:pharmacology; D008564:Membrane Potentials / Q000502:physiology; D018721:Muscarinic Agonists / Q000494:pharmacology*; D018727:Muscarinic Antagonists / Q000494:pharmacology; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D010627:Phenethylamines / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism*; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000502:physiology*; D013449:Sulfonamides / Q000494:pharmacology
D000889:Anti-Arrhythmia Agents; D004232:Diuretics; D018721:Muscarinic Agonists; D018727:Muscarinic Antagonists; D010627:Phenethylamines; D015221:Potassium Channels; D011976:Receptors, Muscarinic; D013449:Sulfonamides; D001285:Atropine; D015761:4-Aminopyridine; D007190:Indapamide; D000109:Acetylcholine; C063533:dofetilide