Zaza A, Kline R P, Rosen M R
Department of Pharmacology, Columbia University, College of Physicians and Surgeons, New York, NY 10032.
Circ Res. 1990 Feb;66(2):416-26. doi: 10.1161/01.res.66.2.416.
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.
大约60%的成年犬浦肯野纤维对α1 - 肾上腺素能刺激有自动节律性降低的反应。最近对分离的浦肯野心肌细胞的研究表明，这种负性变时效应是由Na - K泵的α1 - 肾上腺素能激活引起的。在本研究中，我们评估了：1）Na - K泵激活是否与成年犬浦肯野纤维中α1 - 肾上腺素能刺激的负性变时效应相关；2）α - 激动剂对该泵的作用是直接的还是由细胞内钠活性（aNai）增加介导的。我们使用钠选择性微电极来确定5×10⁻⁹M和5×10⁻⁸M去氧肾上腺素对aNai的影响。去氧肾上腺素使8条浦肯野纤维中的5条自动节律性降低，而另外3条则升高。心率降低总是伴随着aNai的降低（-3.9 mM；p<0.05），而在心率升高的纤维中，aNai没有变化。为了评估在自动节律性无变化的情况下去氧肾上腺素的作用，在起搏期间研究了10条浦肯野纤维。6条纤维中aNai明显降低（-2.8 mM）；另外4条没有变化。去氧肾上腺素的作用被哌唑嗪阻断，但不被普萘洛尔阻断。我们得出结论，α1 - 肾上腺素能刺激降低aNai的作用与Na - K泵的激活一致。此外，α1 - 肾上腺素能刺激的这一作用与其负性变时效应密切相关。
