Riepe M, Hori N, Ludolph A C, Carpenter D O, Spencer P S, Allen C N
Center for Research on Occupational and Environmental Toxicology, Oregon Health Science University, Portland 97201.
Brain Res. 1992 Jul 17;586(1):61-6. doi: 10.1016/0006-8993(92)91371-k.
3-Nitropropionic acid (1 mM), which inhibits succinate dehydrogenase activity and reduces cellular energy, produces in the pyramidal cell layer of the hippocampal region CA1 a hyperpolarization for variable lengths of time before evoking an irreversible depolarization. Hyperpolarization is caused by an increased potassium conductance that is attenuated by glibenclamide (1-10 microM), a selective antagonist of ATP-sensitive potassium channels; in contrast, diazoxide (0.5 mM), an agonist at this channel, induces a hyperpolarization in CA1 neurons of rat hippocampal slices. The transient hyperpolarization after prolonged (ca. 1 h) application of 3-NPA is followed by a depolarization that is incompletely reversed by brief application of the glutamate antagonists (D-2-amino-5-phosphonopentanoic acid (APV), 6,7-dichloroquinoxaline-2,3-dione (CNQX), 3-(+/-)-2-carboxypiperazin-4-yl)propyl-1-phosphonic acid (CPP), 7-chloro-kynurenic acid (7Cl-KYN)). Early application of glibenclamide (within the initial 5 min) blocked or reduced hyperpolarization and accelerated the depolarization. These data suggest that metabolic inhibition by 3-NPA initially activates ATP-sensitive potassium channels. Events other than activation of glutamate receptors participate in the final depolarization resulting from uncoupling of oxidative phosphorylation.
3-硝基丙酸（1毫摩尔）可抑制琥珀酸脱氢酶活性并降低细胞能量，在海马区CA1的锥体细胞层中会产生一段时长可变的超极化，之后才引发不可逆的去极化。超极化是由钾电导增加所致，而这种增加会被格列本脲（1 - 10微摩尔）减弱，格列本脲是ATP敏感性钾通道的选择性拮抗剂；相反，二氮嗪（0.5毫摩尔）作为该通道的激动剂，可在大鼠海马切片的CA1神经元中诱导超极化。在长时间（约1小时）应用3 - NPA后出现的短暂超极化之后会出现去极化，短暂应用谷氨酸拮抗剂（D - 2 - 氨基 - 5 - 膦酰戊酸（APV）、6,7 - 二氯喹喔啉 - 2,3 - 二酮（CNQX）、3 -（±）- 2 - 羧基哌嗪 - 4 - 基）丙基 - 1 - 膦酸（CPP）、7 - 氯犬尿氨酸（7Cl - KYN））并不能完全逆转这种去极化。早期应用格列本脲（在最初5分钟内）可阻断或减少超极化并加速去极化。这些数据表明，3 - NPA引起的代谢抑制最初会激活ATP敏感性钾通道。除了谷氨酸受体激活之外的其他事件参与了由氧化磷酸化解偶联导致的最终去极化过程。
