title: Asynchronous activation of calcium and potassium currents by isoproterenol in canine ventricular myocytes.
abstract: Adrenergic activation of L-type Ca(2+) and various K(+) currents is a crucial mechanism of cardiac adaptation; however, it may carry a substantial proarrhythmic risk as well. The aim of the present work was to study the timing of activation of Ca(2+) and K(+) currents in isolated canine ventricular cells in response to exposure to isoproterenol (ISO). Whole cell configuration of the patch-clamp technique in either conventional voltage clamp or action potential voltage clamp modes were used to monitor I(Ca), I(Ks), and I(Kr), while action potentials were recorded using sharp microelectrodes. ISO (10 nM) elevated the plateau potential and shortened action potential duration (APD) in subepicardial and mid-myocardial cells, which effects were associated with multifold enhancement of I(Ca) and I(Ks) and moderate stimulation of I(Kr). The ISO-induced plateau shift and I(Ca) increase developed faster than the shortening of APD and stimulation of I(Ks) and I(Kr). Blockade of β1-adrenoceptors (using 300 nM CGP-20712A) converted the ISO-induced shortening of APD to lengthening, decreased its latency, and reduced the plateau shift. In contrast, blockade of β2-adrenoceptors (by 50 nM ICI 118,551) augmented the APD-shortening effect and increased the latency of plateau shift without altering its magnitude. All effects of ISO were prevented by simultaneous blockade of both receptor types. Inhibition of phosphodiesterases decreased the differences observed in the turn on of the ISO-induced plateau shift and APD shortening. ISO-induced activation of I(Ca) is turned on faster than the stimulation of I(Ks) and I(Kr) in canine ventricular cells due to the involvement of different adrenergic pathways and compartmentalization.
authors.affiliation: Department of Physiology, Medical and Health Science Center, University of Debrecen, Debrecen, Nagyerdei krt 98, 4012, Hungary.
authors.forename: Ferenc
authors.initials: F
authors.lastname: Ruzsnavszky
authors.forename: Bence
authors.initials: B
authors.lastname: Hegyi
authors.forename: Kornél
authors.initials: K
authors.lastname: Kistamás
authors.forename: Krisztina
authors.initials: K
authors.lastname: Váczi
authors.forename: Balázs
authors.initials: B
authors.lastname: Horváth
authors.forename: Norbert
authors.initials: N
authors.lastname: Szentandrássy
authors.forename: Tamás
authors.initials: T
authors.lastname: Bányász
authors.forename: Péter P
authors.initials: PP
authors.lastname: Nánási
authors.forename: János
authors.initials: J
authors.lastname: Magyar
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D015220:Calcium Channels / Q000187:drug effects*; D004285:Dogs; D005260:Female; D006352:Heart Ventricles / Q000378:metabolism; D007545:Isoproterenol / Q000494:pharmacology*; D008297:Male; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism; D015221:Potassium Channels / Q000187:drug effects*; D011943:Receptors, Adrenergic, beta / Q000502:physiology
chemical_list: D015220:Calcium Channels; D015221:Potassium Channels; D011943:Receptors, Adrenergic, beta; D007545:Isoproterenol