Effect of alpha adrenergic agonists and blockers on Purkinje fiber transmembrane potentials and automaticity in the dog.
Previous studies have shown that alpha adrenergic stimulation can reduce the automaticity of canine Purkinje fibers. In the present study, our interest was to determine whether this is an alpha-1 or alpha-2 adrenergic action. We used standard microelectrode techniques to study the effects of the alpha agonists, phenylephrine and clonidine, and the alpha antagonists, prazosin and yohimbine, on phenylephrine-induced decreases in automaticity. Prazosin and yohimbine, 1 X 10(-5) M, alone, significantly reduced the amplitude and upstroke velocity (Vmax) of stimulated action potentials. In addition, yohimbine, 1 X 10(-5) M, accelerated and prazosin, 1 X 10(-5) M, attenuated repolarization. Prazosin, 1 X 10(-5) M, and yohimbine greater than or equal to 1 X 10(-7) M, alone, decreased automaticity. Phenylephrine, 5 X 10(-8) M, alone, significantly increased the cycle length of automatic Purkinje fibers. The effects of phenylephrine on automaticity were blocked by prazosin but not by yohimbine. Clonidine, alone, 1 X 10(-6) and 1 X 10(-5) M, significantly reduced automaticity, an effect that was not blocked by yohimbine or prazosin. Clonidine, 1 X 10(-6) and 1 X 10(-5) M, also significantly reduced Vmax and prolonged action potential duration of driven Purkinje fibers, an action consistent with direct membrane effects. These experiments suggest that the negative chronotropic effects of phenylephrine on Purkinje fiber automaticity are mediated by alpha-1 adrenergic receptors.
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000818:Animals; D003000:Clonidine / Q000494:pharmacology; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D006329:Heart Conduction System / Q000187:drug effects*; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects; D010656:Phenylephrine / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D011690:Purkinje Fibers / Q000187:drug effects* / Q000502:physiology; D015016:Yohimbine / Q000494:pharmacology
D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D010656:Phenylephrine; D015016:Yohimbine; D003000:Clonidine; D011224:Prazosin