EFFECTS OF GLUCOSE DEPRIVATION ON NMDA-INDUCED CURRENT AND INTRACELLULAR CA2-NIGRA NEURONS( IN RAT SUBSTANTIA)

1. The effects of glucose deprivation on N-methyl-D-aspartate (NMDA)-i nduced current (I-NMDA) and the intracellular free Ca2+ concentration ([Ca2+](i)) in the acutely dissociated rat substantia nigra neurons we re investigated using the nystatin-perforated patch-clamp technique un der voltage clamp and the microfluometry with a fluorescent probe, Ind o-1. 2. Application of NMDA induced a peak and a successive steady-sta te inward current, and an outward current immediately after washout at a holding potential of -40 mV. The amplitudes of the three current co mponents of I-NMDA were increased by increasing the concentrations of NMDA with half-maximum concentrations (EC(50)s) of 1.1 x 10(-4) M, 1.2 x 10(-4) M, and 1.6 x 10(-4) M, respectively. 3. The reversal potenti als of the peak inward and outward currents were -4 +/- 3 (SE) mV and -76 +/- 2 mV, respectively. The latter was close to the theoretical K equilibrium potential (-82 mV). 4. The outward current was potentiate d by increase in extracellular Ca2+ concentration and was blocked by C s+ internal solution and suppressed by 5 x 10(-3) M tetraethylammonium chloride and 10(-7) M charybdotoxin, indicating that it was Ca2+-acti vated K+ current. 5. Application of NMDA increased [Ca2+](i) in a conc entration-dependent manner with an EC(50) of 3.9 x 10(-5) M. 6. Depriv ing the external solution of glucose induced a slowly developing outwa rd current and increased the basal level of [Ca2+](i). It also prolong ed the NMDA-induced outward current without affecting the peak inward current, and prolonged the NMDA-induced increase in [Ca2+](i) without changing the peak [Ca2+](i). 7. These findings suggest that the depriv ation of glucose did not affect the NMDA-induced influx of Ca2+ into t he cells, but it inhibited Ca2+ clearance by affecting the efflux of C a2+ to the extracellular space, reuptake into the intracellular Ca2+ s tores, and/or active extrusion from intracellular stores.