Rainnie D G, Holmes K H, Shinnick-Gallagher P
Department of Pharmacology and Toxicology, University of Texas Medical Branch, Galveston 77555-1031.
J Neurosci. 1994 Nov;14(11 Pt 2):7208-20. doi: 10.1523/JNEUROSCI.14-11-07208.1994.
Glutamate has traditionally been regarded as an excitatory neurotransmitter. Synaptic activation of ionotropic glutamate receptors mediates fast EPSPs in the CNS. Moreover, activation of metabotropic glutamate receptors (mGluRs), which are coupled to second messenger effector systems via GTP-binding proteins (G-proteins), results in the expression of slow EPSPs. We have now examined the response of basolateral amygdala (BLA) neurons to activation of postsynaptic mGluRs. In approximately 78% of BLA neurons examined, activation of postsynaptic mGluRs results in membrane hyperpolarization and an associated decrease in membrane input resistance or a hyperpolarization followed by a depolarization associated with an increase in input resistance. The purpose of this study was to address the mechanisms underlying the membrane hyperpolarization. Here, we report that the ACPD-induced hyperpolarization is insensitive to TTX, is dependent on extracellular K+ concentrations, and has a reversal potential (-84 mV) close to that estimated from the Nernst equation for an increase in a K+ conductance. In addition, the ACPD response is resistant to (1) intracellular chloride loading, (2) the GABAB receptor antagonist CGP55845A, (3) the ACh receptor antagonist atropine, and (4) the ionotropic glutamate receptor antagonists CNQX and APV. These data suggest that the hyperpolarization results from a direct activation of postsynaptic mGluRs on neurons of the BLA. Furthermore, we performed studies that suggest that the hyperpolarization is G-protein mediated and results from activation of a TEA-sensitive, calcium-dependent potassium conductance. The sensitivity of this conductance to thapsigargin further suggests that this response requires the release of calcium from intracellular stores. In summary, these data suggest a role for glutamate as an inhibitory transmitter in the BLA during periods of metabotropic glutamate receptor activation. In nuclei such as the BLA that are exquisitely sensitive to seizure induction, an inhibitory response to glutamate may act to delay the onset of epileptogenesis.
传统上，谷氨酸被视为一种兴奋性神经递质。离子型谷氨酸受体的突触激活介导中枢神经系统中的快速兴奋性突触后电位（fast EPSPs）。此外，代谢型谷氨酸受体（mGluRs）通过鸟苷三磷酸结合蛋白（G蛋白）与第二信使效应系统偶联，其激活会导致缓慢兴奋性突触后电位的产生。我们现在研究了基底外侧杏仁核（BLA）神经元对突触后mGluRs激活的反应。在大约78%被检测的BLA神经元中，突触后mGluRs的激活导致膜超极化以及膜输入电阻的相关降低，或者是超极化后接着出现与输入电阻增加相关的去极化。本研究的目的是探讨膜超极化背后的机制。在此，我们报告，ACPD诱导的超极化对河豚毒素（TTX）不敏感，依赖于细胞外钾离子浓度，并且其反转电位（-84 mV）接近根据能斯特方程估算的钾离子电导增加时的电位。此外，ACPD反应对以下物质具有抗性：（1）细胞内氯化物负载，（2）GABAB受体拮抗剂CGP55845A，（3）乙酰胆碱受体拮抗剂阿托品，以及（4）离子型谷氨酸受体拮抗剂CNQX和APV。这些数据表明，超极化是由BLA神经元上突触后mGluRs的直接激活引起的。此外，我们进行的研究表明，超极化是由G蛋白介导的，并且是由一种对四乙铵（TEA）敏感、钙依赖性钾离子电导的激活所导致的。这种电导对毒胡萝卜素的敏感性进一步表明，这种反应需要从细胞内储存中释放钙。总之，这些数据表明，在代谢型谷氨酸受体激活期间，谷氨酸在BLA中作为一种抑制性递质发挥作用。在诸如BLA这样对癫痫诱导极其敏感的核团中，对谷氨酸的抑制性反应可能起到延迟癫痫发生起始的作用。
