Fade of the response to prolonged glutamate application in the rat hippocampal slice

Abstract

The effect of prolonged glutamate (GLU) application was examined on 60 CA1 pyramidal neurons in the in vitro rat hippocampal slice preparation. Continuous application of L-GLU, either by bath perfusion (0.5-2 mM) of the slices or iontophoresis (200 mM) into the dendritic region of the neurons, elicited a transient depolarization which faded to a mean of 53% of the initial peak amplitude despite continued exposure to the agonist. Membrane depolarization to aspartate (ASP) and the d-isomer of GLU also faded with time. In contrast, the depolarizing response to the excitatory amino acid agonists N-methyl-D,L-aspartate (NMA), quisqualate (QUIS), and kainate (KA) did not fade significantly during continuous application. The fade of the GLU depolarization was not affected by the NMDA antagonist D-2-amino-5-phosphonovalerate (APV) or by blocking synaptic transmission with tetrodotoxin. At the time of maximum fade of the GLU depolarization, there was no change in input resistance or GLU reversal potential. In addition, fade of the response was not a consequence of changes in extracellular potassium concentration, GLU uptake mechanisms, or the electrogenic pump. The most likely explanation for fade is postsynaptic receptor desensitization.

Characterization of a Barium‐sensitive Outward Current following Glutamate Application on Rat Midbrain Dopaminergic Cells

“…Our results agree with those of Nicoll and Alger (1981), which suggested that an increase in potassium conductance underlies the postglutamateinduced hyperpolarization of CA1 neurons. However, it has to be pointed out that, as observed in hippocampal cells (Thompson and Prince, 1986;Cole et aL, 1989), we have seen a reduction or block of the PEAAR and an increase in the membrane depolarizatiod inward current induced by glutamate during the blockade of an ATPdependent electrogenic Na+/K+ pump. The reduction of the PEAAR might result from a positive shift of EK' (Schwindt et al, 1989;Haglund and Schwarzkroin, 1990) and from a prolongation of the decaying phase of the glutamate-induced response subsequent to the inhibition of the Naf/K+ pump, which could mask the occurrence of an overlapping PEAAR.…”

“…Since this PEAAR was not observed without a preceding depolarizatiodinward current, we argue that the previous response is necessary for its development. ation after EAA exposure has already been reported to occur in CAI hippocampal (Nicoll and Alger, 1981;Thompson and Prince, 1986;Cole et al, 1989) and cortical cells (Mistry and Hablitz, 1990). Two different mechanisms have been suggested to account for it: activation of an electrogenic sodium pump (Thompson and Prince, 1986;Cole et al, 1989) and an increase in a Ca2+-activated K ' conductance (Nicoll and Alger, 1981).…”

“…ation after EAA exposure has already been reported to occur in CAI hippocampal (Nicoll and Alger, 1981;Thompson and Prince, 1986;Cole et al, 1989) and cortical cells (Mistry and Hablitz, 1990). Two different mechanisms have been suggested to account for it: activation of an electrogenic sodium pump (Thompson and Prince, 1986;Cole et al, 1989) and an increase in a Ca2+-activated K ' conductance (Nicoll and Alger, 1981). The increase in membrane conductance, the decrease in amplitude with membrane hyperpolarization and the reversal potential at different concentrations of extracellular potassium suggest that an increase in K+ permeability could sustain the PEAAR in the dopaminergic cells.…”

Deficits in ERK and CREB activation in the hippocampus after traumatic brain injury

“…An average of 8–12 hippocampal slices were generated from each animal. After 2 h of recovery in oxygenated aCSF, we measured levels of phosphorylated, activated ERK in hippocampal slices after brief high KCl depolarization (90 mM) or glutamate stimulation (200 μM) for 30 s. These stimulation paradigms trigger a transient depolarization and brief calcium influx into hippocampal neurons mediated through voltage-gated calcium channels and glutamate receptors [5, 12, 13]. We found that there was a significant increase in ERK activation with KCl treatment or glutamate treatment in hippocampal slices from sham surgery animals, but not from TBI animals at 2 weeks after surgery (Fig.…”

Evidence suggesting creatine as a new central neurotransmitter: presence in synaptic vesicles, release upon stimulation, effects on cortical neurons and uptake into synaptosomes and synaptic vesicles

“…In previous reports, 100 μM to 2 mM of GABA [226][227][228] , 50 μM to 2 mM of Glu 229,230 , 1 to 100 μM of DA 229 , 0.1-100 μM of 5-HT [231][232][233][234][235][236] were bath applied to investigate the physiological functions of neurotransmitters. Our results revealed that, when bath applied, Cr could inhibit cortical neurons at 100 μM within several minutes, with a time course similar to that of 5-HT 237 234 236 and DA 229 , but significantly slower than that of Glu 230 , GABA 48,227 and 5-HT 233 . We speculate that Cr may act on G-protein coupled receptors (GPCRs), rather than the fast acting ligand-gated ion channels, such as AMPA or NMDA receptors for Glu and GABA A receptor for GABA.…”