The functional role of glucose on the excitability and neurotransmission in neurons of rat septal nucleus

体外记录大鼠脑片背外侧隔核(DLSN)和视交叉上核(SCN)神经元的细胞内和全细胞膜片钳记录。降低细胞外葡萄糖产生浓度依赖的超极化，这种超极化与动作电位的自发放电停止相关。低血糖引起的超极化与膜输入阻力降低有关，并且在K~+平衡电位附近发生极性反转。低血糖还导致兴奋性和抑制性突触后电位的抑制。替代2-脱氧-D-葡萄糖，一种抗代谢的葡萄糖底物，模拟了葡萄糖耗竭的影响。甘露七糖(10-20 mM)和二硝基苯酚(50 MM)是氧化磷酸化的有效抑制剂，即使在11 mM的葡萄糖存在下，也能引起膜超极化和突触后电位的抑制。磺脲类药物格列本脲(100um)和甲苯丁胺(1 MM)可部分抑制超极化。用“切片-斑片”技术记录DLSN神经元的降糖外向电流。膜破裂后静息膜电位为-62sy.+-4 mV(n=18)，输入电阻为200-300mOMEGA。通过膜片吸管注射ATP抑制了低血糖引起的外向电流，提示低血糖通过激活依赖于ATP的K^+通道(K^+_lt；ATP&gt；通道)引起外向电流。剥夺葡萄糖至2 mM以下刺激海马伞/穹隆通路所诱发的兴奋性突触后电流(EPSC)。抑制突触后电流(IPSC)和晚期超极化电流(LHC)也可通过降低细胞外葡萄糖而降低。葡萄糖缺乏抑制了GABA诱导的外向电流，而不抑制谷氨酸诱导的内向电流。这些结果表明，葡萄糖调节神经传递。

Intracellular and whole-cell patch-clamp recordings were made from neurons in dorsolateral septal nucleus (DLSN) and suprachiasmatic nucleus (SCN) of rat brain slice, in vitro. Lowering extracellular glucose produced a concentration-dependent hyperpolarization associated with a cessation of the spontaneous firing of action potentials. The hypoglycemia-induced hyperpolarization was associated with decreased input membrane resistance and it reversed in polarity at potential near the K^+ equilibrium potential. Hypoglycemia also caused the depression of excitatory and inhibitory postsynaptic potentials. Substitution of 2-Deoxy-D-glucose, an antimetabolic glucose substrate, mimicked these effects of glucose-depletion. Mannoheptulose (10-20 mM) and dinitrophenol (50 muM), potent inhibitors for oxidative phosphorylation, produced both the membrane hyperpolarization and the inhibition of postsynaptic potentials even in the presence of 11 mM glucose. Sulphonylureas, glibenclamide (100 muM) and tolbutamide (1 mM), partially reduced the hyperpolarization. The hypoglycemic outward current was recorded from DLSN neurons by 'slice-patch' technique. After rupturing patch membrane, resting membrane potential and input resistance were -62 (〕SY.+-.〔) 4 mV (n=18) and 200-300 mOMEGA, respectively. Injection of ATP through patch-pipette inhibited the hypoglycemia-induced outward current, suggesting that the hypoglycemia causes the outward current by activation of ATP-dependent K^+ channels (K^+_<ATP> channels). Deprivation of glucose to less than 2 mM depressed excitatory postsynaptic current (EPSC) evoked by stimulations of fimbria/fornix pathway. Inhibitory postsynaptic current (IPSC) and late hyperpolarizing current (LHC) were also reduced by decreasing extracellular glucose. Glucose-depletion depressed GABA-induced outward currents, while it did not depress glutamate-induced inward currents. These results suggest that glucose regulates neurourotransmission