MECHANISM OF ALPHA-2-ADRENERGIC MODULATION OF CANINE CARDIAC PURKINJEACTION-POTENTIAL

We reported recently that stimulation of postjunctional alpha-2 adrene rgic receptors prolongs the action potential durations (APD) of isolat ed canine Purkinje fibers. With standard microelectrode techniques, we examined the ionic mechanism through which alpha-2 adrenergic stimula tion prolonged Purkinje APD, by measuring the effects of inhibitors of the various plateau currents on the alpha-2-mediated prolongation of APD. The alpha-2-specific agonist UK 14,304 (0.1 mu M) prolonged the P urkinje APD at 50% repolarization and the APD at 90% repolarization, a nd these effects were inhibited by yohimbine (0.1 mu M). The Purkinje APD at 50% repolarization and the APD at 90% repolarization were prolo nged significantly with the transient outward potassium current inhibi tor 4-aminopyridine (1 mM), the rapid component of delayed rectifier p otassium current inhibitor d-sotalol (10 mu m), the slow component of delayed rectifier potassium current inhibitor indapamide (0.1 mu M) an d the chloride current inhibitor mefenamic acid (10 nM) and were short ened significantly with the calcium current inhibitor nifedipine (0.3 mu M). Prolongation of Purkinje APD at 50% repolarization and APD at 9 0% repolarization by UK 14,304 remained intact in the presence of d-so talol, indapamide, mefenamic acid and nifedipine. All of these UK 14,3 04 effects were significantly reversed by yohimbine. Only in the prese nce of 4-aminopyridine did UK 14,304 fail to prolong Purkinje APD. The phase 1 magnitudes of Purkinje action potentials were also significan tly inhibited by UK 14,304. This effect was completely abolished only in the presence of 4-aminopyridine. These results suggest that inhibit ion of the 4-aminopyridine-sensitive transient outward potassium curre nt is the major ionic mechanism by which alpha-2 adrenergic stimulatio n prolongs Purkinje APD.