Dobrev D, Milde A S, Andreas K, Ravens U
Institute of Pharmacology and Toxicology, Faculty of Medicine, University of Technology, Dresden, Germany.
Neuropharmacology. 1998 Aug;37(8):973-82. doi: 10.1016/s0028-3908(98)00103-8.
The present study explored the role of different sub-types of voltage-activated Ca2+ channels (VACCs) in mediating veratridine-evoked [3H]dopamine (DA) release from rat striatal slices. The release of [3H]DA evoked by veratridine (25 microM) decreased by 50.6+/-2.9% (n=8) in the absence of calcium and was completely abolished by 1 microM tetrodotoxin. The L-type Ca2+ channel blockers nifedipine (10 microM), nitrendipine (10 microM), diltiazem (10 microM) and verapamil (10 microM) did not modulate this release. Similarly, [3H]DA release was affected neither by the N-type VACC blocker omega-conotoxin-GVIA (1 microM) nor by the selective P-type channel blockers omega-agatoxin-IVA and omega-agatoxin-TK at low nM concentrations (30 nM), indicating no involvement of N- and P-type Ca2+ channels. In contrast, higher concentrations of omega-agatoxin-IVA that would also inhibit Q-type VACCs, blocked the release of [3H]DA by 27.9+/-8.1% (n=5) and 37.5+/-13.6% (n=3) at 0.3 and 1 microM, respectively. In addition, application of the Q-type Ca2+ channel blocker omega-conotoxin-MVIIC (0.01-3 degrees M) reduced [3H]DA release in a concentration-dependent manner, with maximum inhibition of 35.3+/-4.1% at 3 microM (n=5). On the basis of these results, it is concluded that the Ca2+ channels that participate in veratridine-evoked [3H]DA release are Q-type Ca2+ channels.
本研究探讨了不同亚型的电压门控性Ca2+通道（VACCs）在介导藜芦碱诱发的大鼠纹状体切片[3H]多巴胺（DA）释放中的作用。在无钙条件下，藜芦碱（25μM）诱发的[3H]DA释放减少了50.6±2.9%（n=8），并被1μM河豚毒素完全阻断。L型Ca2+通道阻滞剂硝苯地平（10μM）、尼群地平（10μM）、地尔硫卓（10μM）和维拉帕米（10μM）均未调节这种释放。同样，[3H]DA释放既不受N型VACC阻滞剂ω-芋螺毒素-GVIA（1μM）的影响，也不受低纳摩尔浓度（30 nM）的选择性P型通道阻滞剂ω-阿加毒素-IVA和ω-阿加毒素-TK的影响，这表明N型和P型Ca2+通道未参与其中。相比之下，更高浓度的ω-阿加毒素-IVA（也会抑制Q型VACCs）在0.3和1μM时分别阻断了[3H]DA释放的27.9±8.1%（n=5）和37.5±13.6%（n=3）。此外，应用Q型Ca2+通道阻滞剂ω-芋螺毒素-MVIIC（0.01 - 3μM）以浓度依赖性方式降低了[3H]DA释放，在3μM时最大抑制率为35.3±4.1%（n=5）。基于这些结果，得出结论：参与藜芦碱诱发的[3H]DA释放的Ca2+通道是Q型Ca2+通道。
