Bergquist F, Jonason J, Pileblad E, Nissbrandt H
Institute of Physiology and Pharmacology, Department of Pharmacology, Göteborg University, Sweden.
J Neurochem. 1998 Apr;70(4):1532-40. doi: 10.1046/j.1471-4159.1998.70041532.x.
The pivotal role for voltage-sensitive calcium channels in initiating synaptic transmitter release is undisputed, but it is only partly known to what extent the different subtypes contribute in vivo. Their importance for the dendritic release of dopamine has not been investigated in vivo previously. To evaluate comprehensively the relative importance of different voltage-sensitive calcium channel subtypes for striatal dopamine release, and to further investigate the mechanism of dendritic dopamine release in the reticulate part of substantia nigra, dopamine was measured by in vivo microdialysis in the striatum or substantia nigra of awake rats. The calcium channel blockers nimodipine, omega-conotoxin-GVIA, omega-agatoxin-IVA, and neomycin were administered locally through the dialysis probes and compared with calcium-free perfusion. Results indicate that dopamine release in the striatum is mainly dependent on N- and P/Q-type channels, but the dendritic dopamine release in the substantia nigra is mediated mainly by some other calcium-dependent mechanism, for example, calcium mobilization through T-, O-, or R-type calcium channels. A portion of the dendritic release is calcium independent but can be inhibited partially by neomycin, which might suggest a role for inositol 4,5-bisphosphate breakdown products.
电压敏感钙通道在启动突触递质释放中起关键作用，这一点毫无争议，但不同亚型在体内的贡献程度尚不完全清楚。此前尚未在体内研究它们对多巴胺树突状释放的重要性。为了全面评估不同电压敏感钙通道亚型对纹状体多巴胺释放的相对重要性，并进一步研究黑质网状部树突状多巴胺释放的机制，通过对清醒大鼠纹状体或黑质进行体内微透析来测量多巴胺。钙通道阻滞剂尼莫地平、ω-芋螺毒素-GVIA、ω-阿加毒素-IVA和新霉素通过透析探针局部给药，并与无钙灌注进行比较。结果表明，纹状体中的多巴胺释放主要依赖于N型和P/Q型通道，但黑质中的树突状多巴胺释放主要由其他一些钙依赖机制介导，例如通过T型、O型或R型钙通道的钙动员。一部分树突状释放不依赖钙，但可被新霉素部分抑制，这可能提示肌醇4,5-二磷酸分解产物的作用。
