title: Muscarinic-activated potassium current mediates the negative chronotropic effect of pilocarpine on the rabbit sinoatrial node.
abstract: Pilocarpine is a nonspecific agonist of muscarinic receptors which was recently found to activate the M(2) receptor subtype in a voltage-dependent manner. The purpose of our study was to investigate the role of the acetylcholine (muscarinic)-activated K(+) current (I (KACh)) on the negative chronotropic effect of pilocarpine in rabbit sinoatrial node. In multicellular preparations, we studied the effect of pilocarpine on spontaneous action potentials. In isolated myocytes, using the patch clamp technique, we studied the effects of pilocarpine on I (KACh). Pilocarpine produced a decrease in spontaneous frequency, hyperpolarization of the maximum diastolic potential, and a decrease in the diastolic depolarization rate. These effects were partially antagonized by tertiapin Q. Cesium and calyculin A in the presence of tertiapin Q partially prevented the effects of pilocarpine. In isolated myocytes, pilocarpine activated the muscarinic potassium current, I (KACh) in a voltage-dependent manner. In conclusion, the negative chronotropic effects of pilocarpine on the sinatrial node could be mainly explained by activation of I (KACh).
authors.affiliation: Facultad de Veterinaria y Zootecnia, Universidad de Colima, Avenida 25 de Julio 965, Colima, Mexico.
authors.forename: Martín
authors.initials: M
authors.lastname: Rodríguez-Martínez
authors.forename: Iván A
authors.initials: IA
authors.lastname: Aréchiga-Figueroa
authors.forename: Eloy G
authors.initials: EG
authors.lastname: Moreno-Galindo
authors.forename: Ricardo A
authors.initials: RA
authors.lastname: Navarro-Polanco
authors.forename: José A
authors.initials: JA
authors.lastname: Sánchez-Chapula
mesh_terms: D000109:Acetylcholine / Q000378:metabolism*; D000200:Action Potentials / Q000187:drug effects*; D000818:Animals; D001514:Bee Venoms / Q000494:pharmacology; D002586:Cesium / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015640:Ion Channel Gating / Q000187:drug effects; D008387:Marine Toxins; D018721:Muscarinic Agonists / Q000494:pharmacology*; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism; D010080:Oxazoles / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D010862:Pilocarpine / Q000494:pharmacology*; D011188:Potassium / Q000378:metabolism*; D026902:Potassium Channel Blockers / Q000494:pharmacology; D015221:Potassium Channels / Q000378:metabolism*; D011817:Rabbits; D012849:Sinoatrial Node / Q000187:drug effects* / Q000502:physiology
chemical_list: D001514:Bee Venoms; D004791:Enzyme Inhibitors; D008387:Marine Toxins; D018721:Muscarinic Agonists; D010080:Oxazoles; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D010862:Pilocarpine; D002586:Cesium; C029738:tertiapin; C059041:calyculin A; D000109:Acetylcholine; D011188:Potassium