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

Area of Science:

• Cardiovascular Physiology
• Cardiac Electrophysiology
• Pharmacology

Background:

• Alpha-adrenergic agonists prolong action potential duration (APD) in the canine ventricle.
• This effect appears independent of I(to) inhibition, suggesting alternative repolarization mechanisms.
• The study investigates phenylephrine's impact on APD and repolarizing currents in canine myocytes.

Purpose of the Study:

• To determine the effect of phenylephrine on action potential duration (APD) in canine epicardial myocytes.
• To investigate the influence of phenylephrine on the repolarizing currents I(to) and I(K) in canine cardiac cells.
• To elucidate the specific components of I(K) affected by phenylephrine, particularly I(Ks) and I(Kr).

Main Methods:

• Whole-cell voltage clamp technique applied to isolated canine epicardial and Purkinje myocytes.
• Measurement of action potential duration (APD) and notch amplitude.
• Assessment of the effects of varying phenylephrine concentrations on I(to), I(Kr), and I(Ks) currents.

Main Results:

• Phenylephrine (0.1 microM) increased APD by 13% in canine epicardial cells without altering the action potential notch.
• Phenylephrine did not affect I(to) in epicardial myocytes but inhibited I(to) in Purkinje myocytes (reduced to 69%).
• Phenylephrine inhibited I(K) in epicardial cells, specifically reducing the I(Ks) component to 81% of control, while I(Kr) remained unaffected.

Conclusions:

• Alpha-adrenergic prolongation of repolarization in canine epicardium is not mediated by I(to) inhibition.
• Reduction of the I(Ks) current significantly contributes to phenylephrine's effect on canine epicardial repolarization.
• Differential effects of phenylephrine on I(to) in epicardial versus Purkinje myocytes suggest regional variations in canine cardiac electrophysiology and signaling.