Asynchronous activation of calcium and potassium currents by isoproterenol in canine ventricular myocytes

作者：Ruzsnavszky Ferenc; Hegyi Bence; Kistamas Kornel; Vaczi Krisztina; Horvath Balazs; Szentandrassy Norbert; Banyasz Tamas; Nanasi Peter P^*; Magyar Janos

来源：Naunyn-Schmiedeberg's Archives of Pharmacology, 2014, 387(5): 457-467.

DOI：10.1007/s00210-014-0964-6

• Adrenergic activation
• Action potential duration
• Calcium current
• Potassium currents
• Signal transduction
• Dog myocytes

Adrenergic activation of L-type Ca2+ 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 Ca2+ 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 beta(1)-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 beta(2)-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.

• 出版日期2014-5