Riveros N, Orrego F
Neuroscience. 1986 Mar;17(3):541-6. doi: 10.1016/0306-4522(86)90029-1.
N-Methyl-DL-aspartate, L-glutamate, kainate and DL-homocysteate were found to increase the initial rate and the maximal uptake of 45Ca into the non-inulin space of rat brain cortex slices incubated in vitro. The N-methylaspartate-stimulated calcium uptake was blocked by cadmium and cobalt ions, but not by the organic calcium channel blocker nifedipine or by tetrodotoxin, both of which stimulated the N-methylaspartate-independent calcium influx. gamma-Aminobutyrate increased the spontaneous calcium influx, and also reduced that stimulated by N-methylaspartate to the same level, as found with gamma-aminobutyrate alone. Adenosine (1-100 microM), ethanol (0.1 M), pentobarbital (10-100 microM) and morphine (0.2 mM), were unable to inhibit the N-methylaspartate-activated calcium influx. Ethanol (0.1 M), had no effect on the glutamate- or kainate-activated calcium influx. These findings suggest that the excitatory amino acids, because of their neuronal depolarizing action in brain cortex, lead to the opening of voltage-sensitive calcium channels, which may be blocked by cadmium, but not by the organic calcium channel antagonist, nifedipine. The activation of calcium channels by the excitatory amino acid N-methylaspartate, was entirely unaffected by the depressants ethanol, pentobarbital or morphine, or by the endogenous inhibitory substance, adenosine, thus suggesting that their inhibitory or depressant effects occur through interference with a neuronal mechanism unrelated to the one studied here. gamma-Aminobutyrate, on the other hand, considerably inhibited N-methylaspartate-induced calcium uptake, an effect interpreted as due to a gamma-aminobutyrate-induced increase in chloride conductance, that "clamps" the membrane potential and does not allow further depolarization by N-methylaspartate.
已发现 N-甲基-DL-天冬氨酸、L-谷氨酸、海人藻酸和 DL-高半胱氨酸可提高体外培养的大鼠脑皮质切片非菊糖空间中 45Ca 的初始摄取速率和最大摄取量。N-甲基天冬氨酸刺激的钙摄取被镉离子和钴离子阻断，但不被有机钙通道阻滞剂硝苯地平或河豚毒素阻断，这两种物质均可刺激非 N-甲基天冬氨酸依赖性钙内流。γ-氨基丁酸增加了自发性钙内流，并且还将 N-甲基天冬氨酸刺激的钙内流降低到与单独使用γ-氨基丁酸时相同的水平。腺苷（1 - 100 μM）、乙醇（0.1 M）、戊巴比妥（10 - 100 μM）和吗啡（0.2 mM）均无法抑制 N-甲基天冬氨酸激活的钙内流。乙醇（0.1 M）对谷氨酸或海人藻酸激活的钙内流没有影响。这些发现表明，兴奋性氨基酸由于其在脑皮质中的神经元去极化作用，导致电压敏感性钙通道开放，该通道可能被镉阻断，但不被有机钙通道拮抗剂硝苯地平阻断。兴奋性氨基酸 N-甲基天冬氨酸对钙通道的激活完全不受抑制剂乙醇、戊巴比妥或吗啡或内源性抑制物质腺苷的影响，因此表明它们的抑制或镇静作用是通过干扰与本文所研究机制无关的神经元机制而发生的。另一方面，γ-氨基丁酸显著抑制 N-甲基天冬氨酸诱导的钙摄取，这一效应被解释为是由于γ-氨基丁酸诱导的氯离子电导增加，从而“钳制”膜电位，不允许 N-甲基天冬氨酸进一步使膜去极化。
