Han X Q, Ferrier G R
Department of Pharmacology, Dalhousie University, Halifax, Nova Scotia, Canada.
J Mol Cell Cardiol. 1991 May;23(5):551-62. doi: 10.1016/0022-2828(91)90047-p.
Catecholamines increase the amplitudes of oscillatory afterpotentials (OAP) and peak magnitude of the transient inward current (Iti) responsible for OAP. The objectives of this study were to determine whether beta-adrenoceptor stimulation can induce Iti, and to determine the mechanism by which beta-adrenoceptor stimulation increases the magnitude of Iti. Experiments were performed using standard two electrode voltage--clamp techniques in isolated rabbit Purkinje fibers. Holding potential was either -50 or -80 mV. The Iti was elicited by repolarizing steps, following 1.5 or 3 s activating steps to potentials near 0 mV. Isoproterenol (ISO) failed to induce the Iti at concentrations from 10(-8) to 10(-6)M. However ISO (10(-7)M) significantly increased peak magnitude of spontaneously occurring Iti (P less than 0.05), or Iti induced by acetylstrophanthidin (AS) (P less than 0.05). ISO also shifted the minimum activation voltage 10 mV more negative (P less than 0.05). The current-voltage relationship demonstrated that ISO significantly increased the range of potentials over which Iti greater than or equal to 5 nA occurred, but did not significantly shift the voltage at which maximum peak current was observed. Effects of ISO on Iti were blocked by 10(-7)M propranolol or atenolol. Mn2+ (2 mM) or verapamil (2 microM) blocked the slow inward current (Isi) more than 80% before substantially decreasing peak Iti. Either agent blocked stimulation of Isi but not Iti by ISO at 10(-7)M. In contrast, quinacrine (20 microM), an inhibitor of Na(+)-Ca2+ exchange, abolished stimulation of Iti by ISO while having no significant effect on Isi. Our results indicate that beta-adrenoceptor stimulation cannot induce Iti in rabbit Purkinje fibers, but can enhance the Iti induced by other means, by stimulating Na(+)-Ca2+ exchange.
儿茶酚胺可增加振荡后电位（OAP）的幅度以及负责OAP的瞬时内向电流（Iti）的峰值大小。本研究的目的是确定β-肾上腺素能受体刺激是否能诱导出Iti，并确定β-肾上腺素能受体刺激增加Iti大小的机制。实验采用标准的双电极电压钳技术在离体兔浦肯野纤维上进行。钳制电位为-50或-80 mV。Iti通过复极化步骤诱发，在1.5或3秒的激活步骤后将电位接近0 mV。异丙肾上腺素（ISO）在浓度为10^(-8)至10^(-6)M时未能诱导出Iti。然而，ISO（10^(-7)M）显著增加了自发出现的Iti的峰值大小（P<0.05），或由毒毛花苷（AS）诱导的Iti的峰值大小（P<0.05）。ISO还使最小激活电压向更负的方向移动了10 mV（P<0.05）。电流-电压关系表明，ISO显著增加了Iti大于或等于5 nA时的电位范围，但未显著改变观察到最大峰值电流时的电压。ISO对Iti的作用被10^(-7)M的普萘洛尔或阿替洛尔阻断。2 mM的Mn2+或2 μM的维拉帕米在大幅降低Iti峰值之前阻断了超过80%的慢内向电流（Isi）。这两种药物中的任何一种都阻断了ISO对Isi的刺激，但不阻断ISO对10^(-7)M时Iti的刺激。相比之下，钠-钙交换抑制剂奎纳克林（20 μM）消除了ISO对Iti的刺激，而对Isi没有显著影响。我们的结果表明，β-肾上腺素能受体刺激不能在兔浦肯野纤维中诱导出Iti，但可以通过刺激钠-钙交换来增强由其他方式诱导的Iti。
