Williamson A P, Kennedy R H, Seifen E, Lindemann J P, Stimers J R
Department of Pharmacology and Toxicology, University of Arkansas for Medical Sciences, Little Rock 72205.
Am J Physiol. 1993 Apr;264(4 Pt 2):H1315-8. doi: 10.1152/ajpheart.1993.264.4.H1315.
The purpose of this study was to determine if myocardial alpha 1a-and/or alpha 1b-adrenoceptors are involved in the increase in Na-K pump current (Ip) elicited by alpha 1-adrenergic agonists. Single rat ventricular myocytes were isolated by enzymatic disaggregation. The whole cell patch-clamp technique was used to examine dose-dependent effects of phenylephrine (PE) on holding current (Ih) and to determine whether observed actions were mediated via alpha 1a-or alpha 1b-adrenergic receptors. To minimize the contribution of transsar-colemmal currents other than Ip to Ih, membrane voltage was held constant -40 mV, and cells were maintained in a Ca-free perfusate containing 1 mM Ba and 0.1 mM Cd. All experiments were conducted in the presence of 3 microM nadolol. PE elicited dose-dependent increases in Ih, with a peak effect of 0.57 +/- 0.03 pA/pF observed at 30 microM. The response to PE was dose dependently inhibited by prazosin and chloroethylclonidine and was totally eliminated by 1 mM ouabain. When used at doses selective for the alpha 1a-subtype, WB4101 failed to significantly antagonize the action of PE. These data suggest that the observed alpha 1-adrenoceptor-mediated increase in Ih in isolated rat ventricular myocytes is the result of an increase in Ip effected via stimulation of alpha 1b-adrenergic receptors.
本研究的目的是确定心肌α1a - 和/或α1b - 肾上腺素能受体是否参与α1 - 肾上腺素能激动剂引起的钠钾泵电流(Ip)增加。通过酶解分离单个大鼠心室肌细胞。采用全细胞膜片钳技术检测去氧肾上腺素(PE)对钳制电流(Ih)的剂量依赖性影响,并确定观察到的作用是否通过α1a - 或α1b - 肾上腺素能受体介导。为了最小化除Ip之外的跨膜电流对Ih的贡献,将膜电压保持在 - 40 mV恒定,并将细胞置于含有1 mM Ba和0.1 mM Cd的无钙灌流液中。所有实验均在3 μM纳多洛尔存在下进行。PE引起Ih的剂量依赖性增加,在30 μM时观察到的峰值效应为0.57±0.03 pA/pF。对PE的反应被哌唑嗪和氯乙可乐定剂量依赖性抑制,并被1 mM哇巴因完全消除。当以对α1a亚型有选择性的剂量使用时,WB4101未能显著拮抗PE的作用。这些数据表明,在分离的大鼠心室肌细胞中观察到的α1 - 肾上腺素能受体介导的Ih增加是通过刺激α1b - 肾上腺素能受体导致Ip增加的结果。