Glutamate probabilities

It is difficult to specify the functional role of synthetic enzymes for glutamate in the CNS, partly becau.se glutamate is not only an excitatory neurotransmitter but also a general metabolic substrate. However, excitatory neurons appear to use glutamine as a precursor of transmitter glutamate, probably because glutaminase reaction that produces glutamate from... 

Figure 30-12. Intermediates in tyrosine catabolism. Carbons are numbered to emphasize their ultimate fate. (a-KG, a-ketoglutarate Glu, glutamate PLP, pyridoxal phosphate.) Circled numerals represent the probable sites of the metabolic defects in type II tyrosinemia neonatal tyrosinemia alkaptonuria and 0 type I tyrosinemia, or tyrosinosis.

The NRl family is composed of one subunit with nine different alternatively spliced variants. Block by NMDA channel blockers such as ketamine, MK-801 and phencyclidine is affected by which splice variant of the NRl subunit is involved, probably because the NRl splice variant affects the kinetics of channel activation (the effectiveness of any channel blocker being dependent on how much the channel is open). The glycine binding site is on the NRl subunit and the glutamate binding site is on the NR2 and NR3 subunits. 

Figure 13.3 Whole-cell patch-clamp recordings of excitatory postsynaptic currents (EPSCs) from dorsal horn neurons of rat (prenatal P2-13) spinal cord slices. The normal evoked EPSC of about 160pA obtained by focal stimulation of nearby tissue was dramatically reduced by addition of a cocktail (CABS) of CNQX 10 pM, D-APV 50 pM, bicuculline 10 pM and strychnine 5 pM to block glutamate, GABAa and glycine receptors. The small residual EPSC shown was blocked by the ATP P2 receptor antagonist suramin and is therefore probably mediated by released ATP. (Prom Bardoni et al. 1997 and reproduced by permission of the Journal of Neuroscience)...

Status epilepticus occurs because the brain fails to stop an isolated seizure. The exact reason for this failure is unknown and probably involves many mechanisms. A seizure is likely to occur due to a mismatch of excitatory and inhibitory neurotransmitters in the brain. The primary excitatory neurotransmitter in the brain is glutamate. Glutamate stimulates postsynaptic N-methyl-D-aspartate (NMDA) receptors in the brain, causing an influx of calcium into the cells and depolarization of the neuron. Sustained depolarization may maintain SE and eventually cause neuronal injury and death.7 The primary... 

Fig. 21.14. Isolated inside-out patch from pharyngeal muscle with a patch potential of +50 mV and 800 pM glutamate present in the patch pipette shows the opening of two Glu-CI channels. The addition of 1 pM ivermectin to the bath and thus to the inside of the patch produces (in the same patch) opening of up to three Glu-CI channels simultaneously. Ivermectin increases the probability of opening of Glu-CI channels already opening in the presence of glutamate.

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