Jeong Seong-Woo, Park Byong-Gon, Park Jin-Yong, Lee Joong-Woo, Lee Jung-Ha
Department of Physiology, Yonsei University, Wonju College of Medicine, Ilsan-Dong 162, Wonju, Kangwon-Do, Seoul, Korea.
Neuroreport. 2003 Aug 6;14(11):1537-40. doi: 10.1097/00001756-200308060-00028.
We tested divalent metals including Cu2+, Pb2+, and Zn2+ to determine their pharmacological profiles for blockade of cloned T-type Ca2+ channels (alpha1G, alpha1 H, and alpha1I). Effects of the metals were also evaluated for native low and high voltage-activated Ca2+ channels in rat sympathetic pelvic neurons. Cu2+ and Zn2+ blocked three T-type channel isoforms in a concentration-dependent manner with a higher affinity for alpha1H currents (IC50 = 0.9 microM and 2.3 microM). In pelvic neurons, only Zn2+ showed strong selectivity for T-type Ca2+ currents over high voltage-activated Ca2+ currents. Conversely, Pb2+ block on Ca2+ channels did not show distinctive selectivity. Taken together, these results suggest that besides Ni2+, Cu2+ and Zn2+ can be used as selective blockers of alpha1 H at low concentrations.
我们测试了二价金属离子，包括Cu2+、Pb2+和Zn2+，以确定它们对克隆的T型Ca2+通道（α1G、α1H和α1I）的阻断药理学特征。还评估了这些金属离子对大鼠交感盆腔神经元中天然的低电压和高电压激活Ca2+通道的影响。Cu2+和Zn2+以浓度依赖性方式阻断三种T型通道亚型，对α1H电流具有更高的亲和力（IC50分别为0.9 microM和2.3 microM）。在盆腔神经元中，只有Zn2+对T型Ca2+电流表现出比对高电压激活Ca2+电流更强的选择性。相反，Pb2+对Ca2+通道的阻断没有表现出明显的选择性。综上所述，这些结果表明，除了Ni2+之外，Cu2+和Zn2+在低浓度时可用作α1H的选择性阻断剂。
