GABA-Mediated Inhibition of Glutamate Release During Ischemia in Substantia Gelatinosa of the Adult Rat

Abstract

An ischemia-induced change in glutamatergic transmission was investigated in substantia gelatinosa (SG) neurons of adult rat spinal cord slices by use of the whole cell patch-clamp technique; the ischemia was simulated by superfusing an oxygen- and glucose-free medium (ISM). Following ISM superfusion, 21 of 37 SG neurons tested produced an outward current (23 +/- 4 pA at a holding potential of -70 mV), which was followed by a slow and subsequent rapid inward current; the remaining neurons had only inward currents. During such a change in holding currents, spontaneous excitatory postsynaptic currents (EPSCs) were remarkably decreased in a frequency with time (half-decay time of the frequency: about 65 s). The frequency of spontaneous EPSCs was reduced to 28 +/- 13% (n = 37) of the control level during the generation of the slow inward current (about 4 min after the beginning of ISM superfusion) without a change in the amplitude of spontaneous EPSCs. When ISM was superfused together with either bicuculline (10 microM) or CGP35348 (20 microM; GABA(A) and GABA(B) receptor antagonists, respectively), spontaneous EPSC frequency reduced by ISM recovered to the control level and then the frequency markedly increased [by 325 +/- 120% (n = 22) and 326 +/- 91% (n = 17), respectively, 4 min after ISM superfusion]; this alteration in the frequency was not accompanied by a change in spontaneous EPSC amplitude. Superfusing TTX (1 microM)-containing ISM resulted in a similar recovery of spontaneous EPSC frequency and following increase (by 328 +/- 26%, n = 12) in the frequency; strychnine (1 microM) did not affect ISM-induced changes in spontaneous EPSC frequency (n = 5). It is concluded that the ischemic simulation inhibits excitatory transmission to SG neurons, whose action is in part mediated by the activation of presynaptic GABA(A) and GABA(B) receptors, probably due to GABA released from interneurons as a result of an ischemia-induced increase in neuronal activities. This action might protect SG neurons from an excessive excitation mediated by L-glutamate during ischemia.

Adenosine modulates excitatory synaptic transmission and suppresses neuronal death induced by ischaemia in rat spinal motoneurones

“…We further investigated the effects of adenosine or adenosine receptor agonists on ischaemiainduced neuronal death. In the present study, ischaemia was simulated by superfusing an oxygen-and glucose-deprived medium (ISM), which has been well established in spinal and brain slices [30,49,50]. ISM superfusion for several minutes induced an agonal inward current in lamina IX neurones, as we demonstrated previously [36,37].…”

Ischemic preconditioning ameliorates excitotoxicity by shifting glutamate/γ‐aminobutyric acid release and biosynthesis

“…In their study, the time window between preconditioning and lethal ischemic insult was 4 days, in contrast to our study. Matsumoto et al (2003) found that OGD inhibits excitatory transmission to substantia gelatinosa neurons. By using GABA A and GABA B receptor antagonist they showed that the effect was in part mediated by the activation of presynaptic GABA receptors.…”

Regulation of extracellular glutamate levels in the long-term anoxic turtle striatum: coordinated activity of glutamate transporters, adenosine, KATP+ channels and GABA

“…This is based upon (a) activation of either adenosine receptors, K ATP + channels or GABA A receptors, in the normoxic turtle brain, is able to inhibit glutamate release to levels identical to that seen with the onset of anoxia and (b) inhibiting adenosine receptors and K ATP + channels, in the anoxic turtle brain, is able to increase the rate of glutamate release to normoxic levels. In the mammalian brain each of these pathways have been shown to regulate glutamate release [24][25][26].…”