Mechanism of alpha-2 adrenergic modulation of canine cardiac Purkinje action potential.
We reported recently that stimulation of postjunctional alpha-2 adrenergic receptors prolongs the action potential durations (APD) of isolated canine Purkinje fibers. With standard microelectrode techniques, we examined the ionic mechanism through which alpha-2 adrenergic stimulation 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 microM) prolonged the Purkinje APD at 50% repolarization and the APD at 90% repolarization, and these effects were inhibited by yohimbine (0.1 microM). The Purkinje APD at 50% repolarization and the APD at 90% repolarization were prolonged significantly with the transient outward potassium current inhibitor 4-aminopyridine (1 mM), the rapid component of delayed rectifier potassium current inhibitor d-sotalol (10 microM), the slow component of delayed rectifier potassium current inhibitor indapamide (0.1 microM) and the chloride current inhibitor mefenamic acid (10 nM) and were shortened significantly with the calcium current inhibitor nifedipine (0.3 microM). Prolongation of Purkinje APD at 50% repolarization and APD at 90% repolarization by UK 14,304 remained intact in the presence of d-sotalol, indapamide, mefenamic acid and nifedipine. All of these UK 14,304 effects were significantly reversed by yohimbine. Only in the presence of 4-aminopyridine did UK 14,304 fail to prolong Purkinje APD. The phase 1 magnitudes of Purkinje action potentials were also significantly inhibited by UK 14,304. This effect was completely abolished only in the presence of 4-aminopyridine. These results suggest that inhibition of the 4-aminopyridine-sensitive transient outward potassium current is the major ionic mechanism by which alpha-2 adrenergic stimulation prolongs Purkinje APD.
Lee
H C
HC
Department of Internal Medicine, University of Iowa College of Medicine, Iowa City, USA.
Cai
J J
JJ
Arnar
D O
DO
Shibata
E F
EF
Martins
J B
JB
D000200:Action Potentials / Q000187:drug effects*; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000818:Animals; D000068438:Brimonidine Tartrate; D004285:Dogs; D005260:Female; D006321:Heart / Q000187:drug effects*; D008297:Male; D009543:Nifedipine / Q000494:pharmacology; D011689:Purkinje Cells / Q000187:drug effects*; D011810:Quinoxalines / Q000494:pharmacology; D018341:Receptors, Adrenergic, alpha-2 / Q000187:drug effects*
D000316:Adrenergic alpha-Agonists; D011810:Quinoxalines; D018341:Receptors, Adrenergic, alpha-2; D000068438:Brimonidine Tartrate; D009543:Nifedipine