Electrogenic uptake of sulphur‐containing analogues of glutamate and aspartate by Müller cells from the salamander retina.

Abstract

SUMMARY1. The effect of sulphur-containing analogues of glutamate and aspartate on the membrane current of glial cells was studied by whole-cell clamping Muller cells isolated from the salamander retina.2. L-Cysteic acid (CA), L-cysteinesulphinic acid (CSA), L-homocysteic acid (HCA), L-homocysteinesulphinic acid (HCSA) and S-sulpho-L-cysteine (SC) all evoked an inward membrane current that was large at negative potentials, and was smaller (but did not reverse) at more positive potentials up to + 30 mV.3. Removal of external sodium ions abolished the amino acid-evoked currents. Whole-cell clamping with pipettes containing no potassium led to a rapid suppression of the currents, that did not occur when potassium was included in the pipette.4. The dependence of the currents on sulphur-containing amino acid concentration obeyed first-order Michaelis-Menten kinetics. The current evoked by co-application of L-glutamate and a sulphur-containing analogue was smaller than the sum of the currents produced by glutamate alone and by the sulphur analogue alone.5. These data are consistent with the sulphur amino acid-evoked current being caused by uptake on the electrogenic glutamate uptake carrier, which co-transports an excess of Na+ ions into the cell, and counter-transports one K+ ion out of the cell.

Functional Characterization and In Silico Docking of Full and Partial GluK2 Kainate Receptor Agonists

“…Several of the amino acids examined in this study are endogenous to the CNS and have been previously evaluated as neurotrans- molpharm.aspetjournals.org mitter candidates at glutamatergic synapses. The candidature of sulfur-containing amino acids, which include L-Cys, HC, SSC, and HCSA, was considered after mechanisms that lead to their release, uptake, and responsiveness (see below) were identified (Do et al, 1986;Bouvier et al, 1991). Recent attention has focused on their potent activation of metabotropic glutamate receptors (e.g., Kingston et al, 1998).…”

(1R,3S)‐1‐Aminocyclopentane‐1,3‐dicarboxylic acid (RS‐ACPD) reduces intracellular glutamate levels in astrocytes

“…1999). In addition to glutamate, these transporters also transport aspartate and several sulfur‐containing amino acids (Balcar and Johnston 1972; Bouvier et al . 1991; Schousboe and Westergaard 1995).…”

Neuronal and glial localization of homocysteate-like immunoreactivity in the rat retina

“…Consequently, it could be argued that the HCA released from bipolar and amacrine cells and that possibly synthesized by Mi~ller cells, is accumulated in these glial cells. Under certain circumstances, HCA is released by a calcium-independent mechanism such as reversed operation of the electrogenic glutamate uptake or by exchange on the carrier with uptake of extracellular glutamate (Szatkowski et al, 1990;Bouvier et al, 1991). Finally, the accumulation of HCA in the extracellular space may lead to neuronal damage similar to that observed in the application of HCA to the chick retina and thus HCA may need to be actively removed by M~iller cells, and perhaps also by neurons.…”

“…Thus, they remove K + from the extracellular space, metabolize carbon dioxide and also have uptake mechanisms for neurotransmitters (for reviews see Ripps & Witkovsky, 1985;Newman, 1986Newman, , 1987. In this sense, it has been shown that HCA is taken up into salamander M~iller cells by using the electrogenic glutamate transport mechanism, despite its low affinity for this Na +, K + and voltage dependent glutamate carrier (Bouvier et al, 1991). Consequently, it could be argued that the HCA released from bipolar and amacrine cells and that possibly synthesized by Mi~ller cells, is accumulated in these glial cells.…”