Ionic Basis for Action Potential Prolongation by Phenylephrine in Canine Epicardial Myocytes

Phenylephrine Action on Repolarization. Introduction: In canine ventricle, α-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 he independent of inhibition of I_to. The present study investigated the action of the α-adrenergic agonist phenylephrine on the action potential and the repolarizing currents I_to and I_K in isolated canine epicardial myocytes.

Methods and Results: Isolated cells from canine epicardial tissue, and Purkinje fibers, were studied with the whole cell, voltage clamp method. Phenylephrine 0.1 μM increased APD by 13%± 4% at 90% repolarization without affecting the notch or amplitude. Under voltage clamp, concentrations of phenylephrine as high as 10 μM had no effect on I_tp in canine epicardial myocytes. However, I_to of isolated canine Purkinje myocytes was reduced to 69%± 7% of control by 1 μM phenylephrine. Further studies in canine epicardial myocytes revealed an action of phenylephrine to inhibit I_k, and in particular I_Ks Using a voltage protocol that included a two-step repolarization to separate I_Ks and I_Kr tail components, the largely 1_Ke, component was not significantly affected by 1 μM phenylephrine, whereas the largely I_Ks component was reduced to 81%± 5% of control value.

Conclusion: α-Adrenergic prolongation of repolarization in canine epicardium does not result from inhibition of I_to. Rather, it appears that reduction of I_Ks contributes to the action of phenylephrine. The unresponsiveness of epicardial I_to is not a general characteristic of the canine heart, because Purkinje myocyte I_to was inhibited, suggesting regional differences in the molecular basis of l_to, and/or a-adrenergic signaling in the canine heart.