title: Restoration of transient outward current by norepinephrine in cultured canine cardiac myocytes.
abstract: The mechanism for the reduction of the transient outward K+ current (Ito) in diseased myocardium is unknown. To identify potential mechanisms, the reduction of Ito and its subsequent restoration by norepinephrine (NE) were studied in cultured canine epicardial myocytes. After myocytes were cultured for 9 days (day 9), Ito density was decreased compared with density on the day of isolation (day 0) (3.2 +/- 0.4 vs. 10.4 +/- 0.4 pA/pF; mean +/- SE). The time constant of current decay (taudecay) was increased, the time course of recovery from inactivation was prolonged, and the half-inactivation voltage (V1/2) was shifted to less negative potentials. Exposure of myocytes on day 8 to 1 microM NE or isoproterenol (Iso) for 1 h had no acute effect on Ito but restored Ito density to 7.6 +/- 1.2 or 9.7 +/- 2.3 pA/pF, respectively, on day 9. Recovery from inactivation and taudecay remained slowed, and V1/2 remained shifted to less negative potentials. The effects of NE and Iso were blocked by actinomycin D and were not mimicked by phenylephrine or phorbol ester. A-23187 (1 microM) also restored Ito. Thus beta-adrenergic agonists restored normal Ito density, but not normal Ito kinetics, in cultured epicardial myocytes, possibly via increased intracellular Ca2+ concentration.
authors.affiliation: Department of Physiology, Cornell University, Ithaca, New York 14853-6401, USA.
authors.forename: L M
authors.initials: LM
authors.lastname: Pacioretty
authors.forename: R F
authors.initials: RF
authors.lastname: Gilmour
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D016922:Cellular Senescence; D004285:Dogs; D017136:Ion Transport / Q000187:drug effects; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D009638:Norepinephrine / Q000494:pharmacology*; D011188:Potassium / Q000378:metabolism*; D013564:Sympathetic Nervous System / Q000502:physiology; D013566:Sympathomimetics / Q000494:pharmacology*
chemical_list: D013566:Sympathomimetics; D011188:Potassium; D002118:Calcium; D009638:Norepinephrine