Graham M E, Burgoyne R D
Physiological Laboratory, University of Liverpool, England, U.K.
J Neurochem. 1995 Dec;65(6):2517-24. doi: 10.1046/j.1471-4159.1995.65062517.x.
Using a range of Ca2+ channel blockers we have investigated the Ca2+ channel subtypes that mediate the depolarisation-induced elevation of the intracellular free Ca2+ concentration ([Ca2+]i) and glutamate release from cultured rat cerebellar granule cells. omega-Conotoxin-GVIA had little effect on either the transient or plateau phase of the depolarisation-induced [Ca2+]i rise or on glutamate release, ruling out a significant role for N-type Ca2+ channels. Nifedipine substantially inhibited the initial transient rise in [Ca2+]i and the plateau phase of the [Ca2+]i rise and glutamate release, suggesting the involvement of L-type Ca2+ channels. Both omega-agatoxin and omega-conotoxin-MVIIC also inhibited the transient rise in [Ca2+]i and glutamate release but not the plateau phase of the [Ca2+]i rise. The inhibitions by nifedipine were not increased by coaddition of omega-conotoxin-MVIIC, suggesting overlapping sensitivity to these channel blockers. These data show that glutamate release from granule cells in response to depolarisation with a high KCI level involves Ca2+ currents that are sensitive to nifedipine, omega-agatoxin-IVA, and also omega-conotoxin-MVIIC. The overlapping sensitivity of the channels to these toxins prevents attribution of any of the phases of the [Ca2+]i rise or glutamate release to distinct P-, Q-, or O-type Ca2+ currents.
我们使用了一系列钙离子通道阻滞剂，研究了介导去极化诱导的细胞内游离钙离子浓度（[Ca2+]i）升高以及培养的大鼠小脑颗粒细胞释放谷氨酸的钙离子通道亚型。ω-芋螺毒素-GVIA对去极化诱导的[Ca2+]i升高的瞬态或平台期以及谷氨酸释放几乎没有影响，排除了N型钙离子通道的重要作用。硝苯地平显著抑制了[Ca2+]i的初始瞬态升高以及[Ca2+]i升高的平台期和谷氨酸释放，表明L型钙离子通道参与其中。ω-阿加毒素和ω-芋螺毒素-MVIIC也抑制了[Ca2+]i的瞬态升高和谷氨酸释放，但不影响[Ca2+]i升高的平台期。同时添加ω-芋螺毒素-MVIIC并没有增强硝苯地平的抑制作用，表明对这些通道阻滞剂存在重叠敏感性。这些数据表明，颗粒细胞在高钾水平去极化刺激下释放谷氨酸涉及对硝苯地平、ω-阿加毒素-IVA以及ω-芋螺毒素-MVIIC敏感的钙离子电流。通道对这些毒素的重叠敏感性使得无法将[Ca2+]i升高或谷氨酸释放的任何阶段归因于不同的P型、Q型或O型钙离子电流。
