Ionic basis for action potential prolongation by phenylephrine in canine epicardial myocytes

Introduction: In canine ventricle, alpha-adrenergic agonists prolong action potential duration (APD) without any effect on the action potential notch, suggesting that, in this species, the effect on repolarization might be in dependent of inhibition of I-to. The present study investigated the action of the alpha-adrenergic agonist phenylephrine on the action potential and t he repolarizing currents I-to and I-K in isolated canine epicardial myocyte s. Methods and Results: Isolated cells from canine epicardial tissue, and Purk inje fibers, were studied with the whole cell, voltage clamp method. Phenyl ephrine 0.1 mu M increased APD by 13% +/- 4% at 90% repolarization without affecting the notch or amplitude. Under voltage clamp, concentrations of ph enylephrine as high as 10 mu M had no effect on I-to in canine epicardial m yocytes, However, I-to of isolated canine Purkinje myocytes was reduced to 69% +/- 7% of control by 1 mu M phenylephrine, Further studies in canine ep icardial myocytes revealed an action of phenylephrine to inhibit I-K, and i n particular I-Ks. Using a voltage protocol that included a two-step repola rization to separate I-Ks and I-Kr tail components, the largely I-Kr compon ent was not significantly affected by 1 mu M phenylephrine, whereas the lar gely I-Ks component was reduced to 81% +/- 5% of control value. Conclusion: alpha-Adrenergic prolongation of repolarization in canine epica rdium does not result from inhibition of I-to. Rather, it appears that redu ction of I-Ks contributes to the action of phenylephrine, The unresponsiven ess of epicardial I-to is not a general characteristic of the canine heart, because Purkinje myocyte I-to was inhibited, suggesting regional differenc es in the molecular basis of I-to and/or alpha-adrenergic signaling in the canine heart.