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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

Torres-Jácome, Julián PhD*; Tejeda-Chávez, Hector R. MSc; Rodríguez-Menchaca, Aldo A. MSc; Sánchez-Chapula, José A. MD, PhD; Navarro-Polanco, Ricardo A. PhD

Journal of Cardiovascular Pharmacology:
doi: 10.1097/01.fjc.0000211753.47067.cc
Original Articles
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.

Author Information

*Instituto de Fisiología, Benemérita Universidad Autónoma de Puebla

Unidad de Investigación “Carlos Méndez” del Centro Universitario de Investigaciones Biomédicas de la Universidad de Colima, Colima, Col. México

Supported by SEP-SESIC (Mexico) grant No. 2004-C01-47577 and Fondo Ramon Alvarez-Buylla to RANP (Universidad de Colima, Mexico).

Reprints: Ricardo A. Navarro-Polanco, PhD, Centro Universitario de Investigaciones Biomédicas, Universidad de Colima, Av. 25 de Julio No. 965, Col. Villa San Sebastián, CP 28045, Colima, Col. México (e-mail: magdal@cgic.ucol.mx).

Received for publication January 26, 2006; accepted March 29, 2006

© 2006 Lippincott Williams & Wilkins, Inc.