Cunningham J, Neal M J
Br J Pharmacol. 1981 Jul;73(3):655-67. doi: 10.1111/j.1476-5381.1981.tb16801.x.
1 The mechanisms by which veratridine increases the release of gamma-aminobutyric acid (GABA) from brain slices have been studied.2 Exposure of superfused cerebro-cortical, nigral or cerebellar slices to veratridine (5 muM) or KCl (50 mM) caused large increases in the efflux of [(3)H]-GABA.3 Reduction of the external Ca concentration Ca to zero had strikingly different effects on the veratridine and K-evoked release of [(3)H]-GABA. The K-evoked release from all three areas was greatly reduced in Ca-free medium, but the veratridine-evoked release from cerebeller slices was not affected, and the release of [(3)H]-GABA from cortical and nigral slices was increased three fold. The potentiation of the veratridine evoked release of GABA which occurred in Ca-free medium was not due to the reduction in divalent ions, because it still occurred in medium in which the Ca was replaced by an equivalent amount of Mg.4 The veratridine-evoked release of [(14)C]-glycine from slices of spinal cord was also significantly increased in Ca-free medium. In contrast, the release of cortical [(3)H]-noradrenaline and [(14)C]-acetylcholine caused by the alkaloid was greatly diminished in Ca-free medium.5 The veratridine but not the K-evoked release of [(3)H]-GABA was abolished when the external Na concentration Na was reduced to zero and by tetrodotoxin (TTX) (0.2 muM). Cl-free medium did not affect the veratridine-evoked release of [(3)H]-GABA or its potentiation by Ca-free medium.6 Exposure of the tissue to depolarizing concentrations of external K (K = 120 mM) did not abolish the veratridine evoked release of [(3)H]-GABA or its potentiation by Ca-free medium.7 Pre-incubation of cortical slices with L-2,4, diaminobutyric acid (DABA), or substitution of Na in the superfusion medium with Li, did not affect the veratridine-evoked release of [(3)H]-GABA, indicating that the alkaloid does not stimulate GABA efflux by a carrier-mediated transport process.8 Exposure of the tissue to ruthenium red (10 muM) increased the veratridine evoked release of [(3)H]-GABA in both normal and in Ca-free medium but almost abolished the K-evoked release.9 It is suggested that veratridine causes GABA release by increasing the permeability of the nerve terminals to Na. In normal medium, the resulting influx of Ca(2+) ions through voltage-dependent Ca(2+) channels may be involved in triggering the release of GABA. However, a major part of the GABA efflux appears to be triggered by the release of Ca(2+) ions from intraterminal mitochondria, which results from the increase inNa. Since Ca(2+) ions antagonize the action of veratridine, the potentiation of the drug-evoked release of GABA that occurs in Ca-free medium, might be due to the absence of the antagonistic Ca(2+) ions. The resulting greater increase in Na entry and Ca caused by Ca release from intracellular stores, must presumably more than balance the contribution normally made by any influx of extracellular Ca(2+).
已对藜芦碱增加脑片γ-氨基丁酸（GABA）释放的机制进行了研究。
将灌流的大脑皮质、黑质或小脑切片暴露于藜芦碱（5μM）或氯化钾（50mM）中，会使[³H]-GABA的流出量大幅增加。
将细胞外钙浓度[Ca]ₒ降至零，对藜芦碱和钾诱发的[³H]-GABA释放产生了截然不同的影响。在无钙培养基中，来自所有三个区域的钾诱发释放大幅减少，但小脑切片中藜芦碱诱发的释放不受影响，并且来自皮质和黑质切片的[³H]-GABA释放增加了三倍。在无钙培养基中发生的藜芦碱诱发的GABA释放增强并非由于二价离子的减少，因为在钙被等量镁替代的培养基中仍会发生这种情况。
在无钙培养基中，藜芦碱诱发的脊髓切片中[¹⁴C]-甘氨酸释放也显著增加。相比之下，生物碱引起的皮质[³H]-去甲肾上腺素和[¹⁴C]-乙酰胆碱释放在无钙培养基中大大减少。
当细胞外钠浓度[Na]ₒ降至零并使用河豚毒素（TTX）（0.2μM）时，藜芦碱诱发的[³H]-GABA释放被消除，但钾诱发的释放不受影响。无氯培养基不影响藜芦碱诱发的[³H]-GABA释放或其在无钙培养基中的增强作用。
将组织暴露于去极化浓度的细胞外钾（[K]ₒ = 120mM）不会消除藜芦碱诱发的[³H]-GABA释放或其在无钙培养基中的增强作用。
用L-2,4-二氨基丁酸（DABA）预孵育皮质切片，或在灌流培养基中用锂替代钠，均不影响藜芦碱诱发的[³H]-GABA释放，这表明生物碱不是通过载体介导的转运过程刺激GABA流出。
将组织暴露于钌红（10μM）会增加正常和无钙培养基中藜芦碱诱发的[³H]-GABA释放，但几乎消除了钾诱发的释放。
有人提出，藜芦碱通过增加神经末梢对钠的通透性来导致GABA释放。在正常培养基中，由此产生的钙离子通过电压依赖性钙通道的内流可能参与触发GABA的释放。然而，GABA流出的主要部分似乎是由终末内线粒体释放的钙离子触发的，这是由[Na]i的增加导致的。由于钙离子拮抗藜芦碱的作用，在无钙培养基中发生的药物诱发的GABA释放增强可能是由于缺乏拮抗钙离子。细胞内储存释放的钙导致的钠内流和[Ca]i的更大增加，想必一定超过了细胞外钙内流通常所起的作用。
