| Research Abstract |
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
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