Complications Of Glutamate Synthetase

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After astrocytes remove glutamate from the ECS, glutamate must be isolated and degraded. Glutamate transporters are bidirectional, so intracellular elevations of glutamate levels will lead to an electrochemical gradient-mediated release if the molecule is not destroyed. If glutamate release is unregulated glutamate accumulates in the ECS and impairs the survival of neurons. Glutamate dehydrogenase (GDH) helps degrade glutamate into a-ketoglutarate, an intermediary in the tricarboxylic acid (TCA) cycle (Coulter and Steinhauser, 2015). Superfluous glutamate release depletes the TCA cycle of intermediates and impairs ATP synthesis (Coulter and Eid, 2012). Another degradation enzyme is glutamine synthetase (GS), found predominantly in astrocytes …show more content…
Reestablishing potassium ion levels leads to neuronal hyperpolarization and suppresses synaptic excitation by shortening miniature excitatory postsynaptic currents (mEPSCs). Potassium concentration in the extracellular fluid must be corrected otherwise the gap between threshold potential and the resting membrane potential narrows, activation of transmembrane ion channels, receptors, and transporters are affected, and action potential recovery slows (Wang et al., 2012). High K+ levels can generate epileptic activity in vivo (Steinhäuser and Seifert, 2012). Astrocytic Na+/K+ ATPase and the Na+/K+/Cl- cotransporter NKCC1 play predominant roles in regulating the surge of potassium released to the extracellular fluid during neuronal activity (Coulter and Steinhauser, 2015). Intracellular concentrations of Na+ limit the rate of Na+/K+ ATPase in astrocytes. Astrocytic Ca2+ signaling in vivo stimulated Na+/K+ ATPase by allowing an influx of Na+ into the cell via a Na+/Ca2+ exchanger. Astrocytic Na+/K+ ATPase is highly sensitive to minor increases in K+ concentrations and, once activated, leads to a transient decrease in extracellular potassium ion concentration (Wang et al., 2012), cell swelling, and local depolarization of astrocytes (Steinhäuser and Seifert, 2012). This mechanism rapidly modulates network activity and leads to an improvement in the signal-to-noise ratio of synaptic transmission (Wang et al., 2012). In the rodent hippocampus, the Na+/K+ ATPase pump has a role in clearing the excess potassium ions present after epileptic activity (Coulter and Steinhauser, 2015). However, Ca2+ mediated K+ uptake is impaired once K+ levels are raised to pathological concentrations (Wang et al.,

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