Effects of glucose deprivation on NMDA-induced current and intracellular Ca
2+ in rat substantia nigra neurons.
Nakashima, Yasunori, Hitoshi Ishibashi, Nobutoshi Harata, and Norio Akaike.
Department of Anesthesiology and Critical Care Medicine, and Department of
Physiology, Faculty of Medicine, Kyushu University, 812-82, Japan
.
APStracts 2:0288N, 1995.
SUMMARY AND CONCLUSIONS
1. The effects of glucose deprivation on N -methyl- D -aspartate (NMDA)-
induced current (I NMDA ) and the intracellular free Ca 2+ concentration ([Ca
2+ ] i ) in the acutely dissociated rat substantia nigra neurons were
investigated using the nystatin-perforated patch-clamp technique under
voltage-clamp and the microfluometry with a fluorescent probe, Indo-1. 2.
Application of NMDA induced a peak and a successive steady-state inward
currents, and an outward current immediately after washout at a holding
potential of -40 mV. The amplitudes of the three current components of I NMDA
were increased by increasing the concentrations of NMDA with the half-maximum
concentration (EC 50 ) of 1.1 [lambda] 10 -4 , 1.2 [lambda] 10 -4 and 1.6
[lambda] 10 -4 M, respectively. 3. The reversal potentials of the peak inward
and outward currents were -4 +/- 3 and -76 +/- 2 mV, respectively. The latter
was close to the theoretical K + equilibrium potential (-82 mV). 4. The
outward current was potentiated by increase in extracellular Ca 2+
concentration and was blocked by Cs + -internal solution, suppressed by 5
[lambda] 10 -3 M tetraethylammonium chloride and 10 -7 M charybdotoxin,
indicating that it was Ca 2+ -activated K + current (I K(Ca) ). 5. Application
of NMDA concentration-dependently increased [Ca 2+ ] i with EC 50 of 3.9
[lambda] 10 -5 M. 6. Deprivation of glucose from the external solution induced
a slowly developing outward current and increased the basal level of [Ca 2+ ]
i . It also prolonged the NMDA-induced outward current without affecting the
peak inward current, and prolonged the NMDA-induced increase in [Ca 2+ ] i
without changing the peak [Ca 2+ ] i . 7. These findings suggest that the
deprivation of glucose did not affect the NMDA-induced influx of Ca 2+ into
the cells, but it inhibited Ca 2+ clearance by affecting the efflux of Ca 2+
to the extracellular space, re-uptake into the intracellular Ca 2+ stores,
and/or active extrusion from intracellular stores.
Received 13 April 1995; accepted in final form 12 September 1995.
APS Manuscript Number J244-5.
Article publication pending J. Neurophysiol.
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 31 October 95