Glutamate depolarization evoked

Liachenko S, Tang P, Somogyi GT, Xu Y. (1999). Concentration-dependent isoflurane effects on depolarization-evoked glutamate and GABA outflows from mouse brain slices. Br J Pharmacol. 

B. Depolarization-Evoked Glutamate Release VI. Concluding Remarks... 

The extremely rapid and abrupt recovery which followed the depolarization evoked by glutamate was often associated with a hyperpolarization of the membrane and could, therefore, be due to the spread of glutamate to nearby inhibitory interneurons. However, the hyperpolarization could also have been due to the activation of the sodium pump by the entry of sodium ions (Koike et ai, 1972) during increased levels of firing. 

The depolarization evoked by acetylcholine is also unusual in that the onset and offset are very much slower than that evoked by glutamate (Figs. 33 and 34), and are very much greater than would be explained by the diffusion of substance from the tips of the multibarrelled micropipette to different sites on the same neuron. For instance, in Fig. 34 the ejection of glutamate for rather less than 6 sec produced a clear-cut excitation, whose total duration is of the same order of magnitude, whereas that evoked by... 

T-T. Yang and S.J. Wang. Pyridoxine inhibits depolarization-evoked glutamate release in nerve terminals from rat cerebral cortex A possible neuroprotective mechanism J. Pharmacol. Exp. Therapeutics 331 244-254 (2009). 

Physiological studies have identified both post- and presynaptic roles for ionotropic kainate receptors. Kainate receptors contribute to excitatory post-synaptic currents in many regions of the CNS including hippocampus, cortex, spinal cord and retina. In some cases, postsynaptic kainate receptors are codistributed with AMPA and NMDA receptors, but there are also synapses where transmission is mediated exclusively by postsynaptic kainate receptors for example, in the retina at connections made by cones onto off bipolar cells. Extrasynaptically located postsynaptic kainate receptors are most likely activated by spill-over glutamate (Eder et al. 2003). Modulation of transmitter release by presynaptic kainate receptors can occur at both excitatory and inhibitory synapses. The depolarization of nerve terminals by current flow through ionotropic kainate receptors appears sufficient to account for most examples of presynaptic regulation however, a number of studies have provided evidence for metabotropic effects on transmitter release that can be initiated by activation of kainate receptors. The hyperexcitability evoked by locally applied kainate, which is quite effectively reduced by endocannabinoids, is probably mediated preferentially via an activation of postsynaptic kainate receptors (Marsicano et al. 2003). 

At the calyx of Held in the medial nucleus of the trapezoid body, activation of presynaptic glycine receptors was also shown to facilitate spontaneous glutamate release and to enhance amplitudes of evoked excitatory postsynaptic currents (Turecek and Trussell 2001). The action on spontaneous postsynaptic currents were insensitive towards a blockade of Na+ channels by tetrodotoxin, but abolished by the Ca2+ channel blocker Cd2+. This indicated that glycine acted by causing a depolarization, which was also corroborated by direct voltage measurements. 

Fig. 4. Electrophysiological traces from a prefrontal layer V showing the response to nearby electrical stimulation of corticocortical afferents. Stimulus artifact appears as a vertical line. (1) The fast evoked excitatory postsynaptic current (evEPSC) follows immediately, as depicted by the arrow. Under normal conditions, stimulation at 0.1 Hz evokes only a fast evEPSC. (2) However, after the application of a psychedelic hallucinogen (3 pMDOI, 15 min), stimulation at this frequency almost always evokes both a fast evEPSC and a late evEPSC, as depicted by the arrows. The neuron is voltage-clamped close to its resting potential and was not directly depolarized by DOI. It is not known what type of glutamate release accounts for the late evEPSC. Traces are averages of 10 sweeps taken during each of the conditions.

The net effect of dopamine is thus likely to depend on the degree of activation of D1 and D2 receptors, on the contribution of NMDA and AMPA receptor-operated channels to the synaptic response, and the interplay between VSCCs and synaptic responses. Generally, the D2 effect predominates, i.e. dopamine inhibits depolarization and firing evoked by glutamate (Cepeda et al., 1992, 1993). 

ON and OFF responses of bipolar cells result from the presence of different glutamate receptors in the two cell types. OFF bipolar cells possess KA and AMPA-type ionotropic glutamate receptors, but not NMDA receptors (Thoreson and Witkovsky, 1999). Thus, like horizontal cells, the synapse from cones to OFF bipolar cells is sign-conserving, that is, light-evoked hyperpolarization of the cone reduces the depolarizing influence of AMPA/KA receptors thereby causing the OFF bipolar cell to hyperpolarize. 

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