Sigel E, Baur R
Pharmakologisches Institut, Universität Bern, Switzerland.
Proc Natl Acad Sci U S A. 1988 Aug;85(16):6192-6. doi: 10.1073/pnas.85.16.6192.
Xenopus oocytes were used to study the interaction of neuronal quisqualate receptors with neuronal ion channels. Total mRNA was isolated from chick forebrain and injected into Xenopus oocytes. This technique led to the expression of functional voltage-gated Na+ and Ca2+ channels, of ligand-gated gamma-aminobutyrate and kainate receptor channels, and of quisqualate receptors that could activate endogenous chloride channels by means of inositol trisphosphate-mediated Ca2+ release. Exposure of the oocytes to quisqualate decreased the amplitude of the Na+ current and of the gamma-aminobutyrate type A-gated current and increased the amplitude of the Ba2+ current through Ca2+ channels. This modulation of neuronal ion channels by quisqualate could be mimicked by the protein kinase C activator phorbol 12-myristate 13-acetate and the diacylglycerol analogue 1,2-oleoylacetylglycerol. The kainate-gated channel was not affected by these agents. Phorbol esters that do not activate protein kinase C, alpha-phorbol 12-myristate 13-acetate and alpha-phorbol, were without effect. The inhibitor of protein kinase C, tamoxifen, prevented the modulatory effects of phorbol 12-myristate 13-acetate. The present evidence suggests that the activity of the neuronal Na+ and Ca2+ channels and the ligand-gated gamma-aminobutyrate type A receptor channel are under the control of protein kinase C and that neurotransmitters that activate protein kinase C could profoundly affect neuronal signaling.
非洲爪蟾卵母细胞被用于研究神经元喹啉酸受体与神经元离子通道之间的相互作用。从鸡前脑分离出总mRNA并注射到非洲爪蟾卵母细胞中。该技术导致功能性电压门控Na⁺和Ca²⁺通道、配体门控γ-氨基丁酸和海人藻酸受体通道以及可通过肌醇三磷酸介导的Ca²⁺释放激活内源性氯离子通道的喹啉酸受体的表达。将卵母细胞暴露于喹啉酸会降低Na⁺电流和A型γ-氨基丁酸门控电流的幅度，并增加通过Ca²⁺通道的Ba²⁺电流的幅度。喹啉酸对神经元离子通道的这种调节作用可被蛋白激酶C激活剂佛波醇12-肉豆蔻酸酯13-乙酸酯和二酰基甘油类似物1,2-油酰乙酰甘油模拟。海人藻酸门控通道不受这些试剂的影响。不激活蛋白激酶C的佛波酯，α-佛波醇12-肉豆蔻酸酯13-乙酸酯和α-佛波醇，没有作用。蛋白激酶C抑制剂他莫昔芬可阻止佛波醇12-肉豆蔻酸酯13-乙酸酯的调节作用。目前的证据表明，神经元Na⁺和Ca²⁺通道以及配体门控A型γ-氨基丁酸受体通道的活性受蛋白激酶C的控制，并且激活蛋白激酶C的神经递质可能会深刻影响神经元信号传导。
