Effects of alpha-adrenergic stimulation on intracellular sodium activity and automaticity in canine Purkinje fibers.
Approximately 60% of adult canine Purkinje fibers respond to alpha 1-adrenergic stimulation with a decrease in automaticity. Recent studies of disaggregated Purkinje myocytes have suggested that this negative chronotropic effect results from alpha 1-adrenergic activation of the Na-K pump. In this study we evaluated 1) whether Na-K pump activation is associated with the negative chronotropic effect of alpha 1-adrenergic stimulation in adult canine Purkinje fibers and 2) if the effect of alpha-agonists on the pump is direct or mediated by an increase in intracellular sodium activity (aNai). We used sodium selective microelectrodes to determine the effects of 5 x 10(-9) and 5 x 10(-8) M phenylephrine on aNai. Phenylephrine decreased automaticity in five of eight Purkinje fibers while an increase occurred in the other three. The rate decrease was always accompanied by a decrease in aNai (-3.9 mM; p less than 0.05), whereas in fibers showing an increase in rate, aNai was unchanged. To evaluate the effect of phenylephrine in the absence of changes in automaticity, 10 Purkinje fibers were studied during pacing. A clear-cut reduction in aNai (-2.8 mM) was present in six fibers; no change was seen in the other four. The effect of phenylephrine was blocked by prazosin but not by propranolol. We conclude that the effect of alpha 1-adrenergic stimulation to reduce aNai is consistent with activation of the Na-K pump. Moreover, this action of alpha 1-adrenergic stimulation is closely linked to its negative chronotropic effect.
Zaza
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A
Department of Pharmacology, Columbia University, College of Physicians and Surgeons, New York, NY 10032.
Kline
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Rosen
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D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D004285:Dogs; D005260:Female; D006329:Heart Conduction System / Q000502:physiology*; D007425:Intracellular Membranes / Q000378:metabolism*; D008297:Male; D010656:Phenylephrine / Q000494:pharmacology; D011690:Purkinje Fibers / Q000187:drug effects / Q000502:physiology*; D011942:Receptors, Adrenergic, alpha / Q000502:physiology*; D012964:Sodium / Q000378:metabolism*
D000317:Adrenergic alpha-Antagonists; D000319:Adrenergic beta-Antagonists; D011942:Receptors, Adrenergic, alpha; D010656:Phenylephrine; D012964:Sodium