The cholinomimetic agent bethanechol activates IK(ACh) in feline atrial myocytes.
The effect of the cholinomimetic agent, bethanechol on macroscopic membrane currents was studied in dispersed cat atrial myocytes, using the whole-cell patch-clamp technique. Bethanechol activated an inward rectifying potassium current similar to I(K(ACh)), and a delayed rectifying-like outward current, similar to I(KM3) activated by pilocarpine, choline, and tetramethylammonium, and I(KM4) activated by 4-aminopyridine. The relatively specific muscarinic receptors subtype antagonists methoctramine (M(2)), and tropicamide (M(4)) inhibited both current components induced by bethanechol, suggesting a lack of specificity of these antagonists on cat atrial myocytes. The specific antagonist of M(3) receptors, para-fluoro-hexahydro-siladifenidol did not significantly inhibit the bethanechol-induced currents. In addition, pretreatment with PTX prevented activation of the bethanechol-induced inward and outward currents, suggesting that M(3) receptors are probably not involved in the bethanechol action. The I(K(ACh)) specific blocker tertiapin inhibited both inward rectifying- and delayed rectifying-like currents. These results suggest that both current components result from activation of a single channel type, likely I(K(ACh)).
Benavides-Haro
Dora E
DE
Facultad de Medicina Humana y Ciencias de la Salud, Universidad Autónoma de Zacatecas, Zacatecas, México.
Navarro-Polanco
Ricardo A
RA
Sánchez-Chapula
José A
JA
D000818:Animals; D001464:Barium / Q000494:pharmacology; D001514:Bee Venoms / Q000494:pharmacology; D001569:Benzodiazepines / Q000494:pharmacology; D018723:Bethanechol / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D002415:Cats; D018678:Cholinergic Agents / Q000494:pharmacology*; D003959:Diamines / Q000494:pharmacology; D006325:Heart Atria / Q000166:cytology; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects; D018721:Muscarinic Agonists / Q000494:pharmacology; D018727:Muscarinic Antagonists / Q000494:pharmacology; D032342:Muscle Cells / Q000187:drug effects / Q000378:metabolism*; D010627:Phenethylamines / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D026902:Potassium Channel Blockers / Q000494:pharmacology; D024661:Potassium Channels, Inwardly Rectifying / Q000819:agonists*; D043643:Receptor, Muscarinic M1 / Q000187:drug effects; D043585:Receptor, Muscarinic M2 / Q000187:drug effects; D043587:Receptor, Muscarinic M3 / Q000187:drug effects; D043588:Receptor, Muscarinic M4 / Q000187:drug effects; D013449:Sulfonamides / Q000494:pharmacology; D014331:Tropicamide / Q000494:pharmacology
D001514:Bee Venoms; D018678:Cholinergic Agents; D003959:Diamines; C115921:L 735821; D018721:Muscarinic Agonists; D018727:Muscarinic Antagonists; D010627:Phenethylamines; D010880:Piperidines; D026902:Potassium Channel Blockers; D024661:Potassium Channels, Inwardly Rectifying; D043643:Receptor, Muscarinic M1; D043585:Receptor, Muscarinic M2; D043587:Receptor, Muscarinic M3; D043588:Receptor, Muscarinic M4; D013449:Sulfonamides; D018723:Bethanechol; C058297:4-fluorohexahydrosiladifenidol; D001569:Benzodiazepines; D001464:Barium; C029738:tertiapin; D014331:Tropicamide; C054938:methoctramine; C063533:dofetilide