Zorumski C F, Thio L L, Clark G D, Clifford D B
Department of Psychiatry, Washington University School of Medicine, St. Louis, MO 63110.
Neurosci Lett. 1989 May 8;99(3):293-9. doi: 10.1016/0304-3940(89)90462-x.
Calcium-activated potassium conductances play important roles in modulating neuronal excitability. Indeed, the effects of some neurotransmitters such as acetylcholine and norepinephrine are, in part, due to actions on these conductances. We have found that the N-methyl-D-aspartate (NMDA) class of excitatory amino acid receptors also is coupled to a calcium activated potassium current. In voltage-clamped postnatal rat hippocampal neurons, NMDA responses consist of an initial inward cationic current followed by a slowly developing outward current carried by potassium ions. The slow outward current always follows the inward current, is associated with an increase in membrane conductance and is dependent on the influx of calcium ions. Similar responses are produced by other agonists active at NMDA receptors, including aspartate, glutamate and ibotenate, but are not activated by kainate, quisqualate or alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA). Inhibition of the NMDA gated inward current by a competitive antagonist, 2-amino-5-phosphonovalerate (APV), eliminates the outward current. From these results we conclude that calcium influx through NMDA channels activates a potassium current. The extended time course of this outward current suggests that NMDA receptors may modulate neuronal excitability long after the opening of the NMDA channel.
钙激活钾电导在调节神经元兴奋性方面发挥着重要作用。事实上，一些神经递质如乙酰胆碱和去甲肾上腺素的作用部分归因于对这些电导的影响。我们发现，N-甲基-D-天冬氨酸（NMDA）类兴奋性氨基酸受体也与钙激活钾电流相关联。在电压钳制的新生大鼠海马神经元中，NMDA反应包括一个初始的内向阳离子电流，随后是一个由钾离子携带的缓慢发展的外向电流。缓慢的外向电流总是跟随内向电流，与膜电导的增加相关，并且依赖于钙离子的内流。其他作用于NMDA受体的激动剂，包括天冬氨酸、谷氨酸和鹅膏蕈氨酸，也会产生类似的反应，但不会被海人酸、quisqualate或α-氨基-3-羟基-5-甲基-4-异恶唑丙酸（AMPA）激活。竞争性拮抗剂2-氨基-5-磷酸戊酸（APV）对NMDA门控内向电流的抑制作用消除了外向电流。从这些结果我们得出结论，通过NMDA通道的钙内流激活了钾电流。这种外向电流的延长时间进程表明，NMDA受体可能在NMDA通道开放后很长时间调节神经元兴奋性。
