title: The D3-dopaminergic agonist 7-hydroxy-dipropylaminotetralin (7-OH-DPAT) increases cardiac action potential duration and blocks human ether-a-go-go-related gene K+ channel.
abstract: The D3-dopaminergic agonist (+/-) 7-hydroxy-dipropylaminotetralin (7-OH-DPAT) prolonged cycle length and action potential duration, depolarized maximum diastolic potential, and reduced the upstroke velocity of the action potential of rabbit sinoatrial node cells. These effects were not mediated by D3-dopaminergic receptors. In cat Purkinje fibers, the drug increased action potential duration. In voltage-clamped cat ventricular myocytes, 7-OH-DPAT blocked the rapid component of the delayed rectifier potassium current, IKr. This effect was corroborated in experiments studying the effect of the drug on human Ether-a-go-go-related Gene channels expressed in Xenopus oocytes and in HEK293 cells. We conclude that the direct electrophysiologic effects of 7-OH-DPAT on cardiac tissues are caused by the blockade of the rapid component of the delayed rectifier potassium current, IKr.
authors.affiliation: Instituto de Fisiología, Benemérita Universidad Autónoma de Puebla, Colima, Col. México.
authors.forename: Julián
authors.initials: J
authors.lastname: Torres-Jácome
authors.forename: Hector R
authors.initials: HR
authors.lastname: Tejeda-Chávez
authors.forename: Aldo A
authors.initials: AA
authors.lastname: Rodríguez-Menchaca
authors.forename: José A
authors.initials: JA
authors.lastname: Sánchez-Chapula
authors.forename: Ricardo A
authors.initials: RA
authors.lastname: Navarro-Polanco
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002415:Cats; D002460:Cell Line; D018491:Dopamine Agonists / Q000494:pharmacology*; D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels / Q000037:antagonists & inhibitors / Q000502:physiology; D006321:Heart / Q000187:drug effects / Q000502:physiology; D006801:Humans; D066298:In Vitro Techniques; D008133:Long QT Syndrome; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000502:physiology; D009865:Oocytes / Q000187:drug effects / Q000502:physiology; D011690:Purkinje Fibers / Q000187:drug effects / Q000502:physiology; D011817:Rabbits; D050637:Receptors, Dopamine D3 / Q000819:agonists*; D012849:Sinoatrial Node / Q000187:drug effects / Q000502:physiology; D013764:Tetrahydronaphthalenes / Q000494:pharmacology*; D014981:Xenopus
chemical_list: D018491:Dopamine Agonists; D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels; C000606913:KCNH2 protein, human; D050637:Receptors, Dopamine D3; D013764:Tetrahydronaphthalenes; C031349:7-hydroxy-2-N,N-dipropylaminotetralin