Brain AMPA receptors

The AMPA receptors mediate the majority of fast excitatory neurotransmission in the mammalian brain. The rapid kinetics and the low Ca permeability make these receptors ideal for fast neurotransmission without sufficient changes in the intracellular calcium concentration to activate Ca2+-dependent processes. The NMDA receptors are co-localized with the AMPA receptors on many synapses, but the slow kinetics of the NMDA receptor minimize the receptor activation after a single presynaptic glutamate release where the neuron quickly repolarizes, resulting in Mg2+ block... 

Larson, J., Quach, C.N., LeDuc, B.Q. et al. Effects of an AMPA receptor modulator on methamphet-amine-induced hyperactivity. Brain Res. 738 353, 1996. 

Pellegrini-Giampietro DE, Bennett MVL, Zukin RS (1992) Are Ca-2-i--permeable kainate/ AMPA receptors more abundant in immature brain. Neurosci Lett 144 65-69 Persson J, Hasselstrom J, Wiklund B, et al (1998) The analgesic effect of racemic ketamine in patients with chronic ischemic pain due to lower extremity arteriosclerosis obliterans. Acta Anaesthesiol Scand 42 750-758... 

Cyr, M. Ghribi, O. Thibault, C. Morissette, M. Landry, M. di Paolo, T. Ovarian steroids and selective estrogen receptor modulators activity on rat brain NMDA and AMPA receptors. Brain Res. Rev. 2001, 37(1—3), 153—161. 

The stargazer mutant mouse is ataxic and epileptic. It lacks functional AMPA receptors (Fig. 30-1), which apparently are not delivered successfully to the synapses in the cerebellum in which they function.380 386 Mutation of a transmembrane protein stargazin, which may interact with the AMP receptor, causes the symptoms.457 458 NMDA receptors (Fig. 30-20) are involved in synapse formation in the brain. Filopodial extensions on dendrites, triggered by electrical activity, are essential for synapse formation,459 which occurs rapidly.4593 Activation of NMDA receptors is apparently also necessary.379 460 Without this stimulation the excitatory glutamatergic neurons of the developing brain undergo apoptosis. 

Structure and Distribution of AMPA Receptor Subunits in Brain... 

Sun H., Kawahara Y., Ito K., Kanazawa I., and Kwak S. (2005). Expression profile of AMPA receptor subunit mRNA in single adult rat brain and spinal cord neurons in situ. Neurosci. Res. 52 228-234. 

Varga V., Jenei Z., Janaky R., Saransaari P., and Oja S. S. (1997). Glutathione is an endogenous ligand of rat brain N-methyl-D-aspartate (NMDA) and 2-ainino-3-hydroxy-5-metliyl-4-isoxazolepropionate (AMPA) receptors. Neurochem. Res. 22 1165-1171. 

Another mechanism of synaptic dysfunction in AD may involve amyloid ft peptide (Aft a 40 to 42 amino acid peptide). A marked increase in Aft levels occurs in brain tissue from AD patients. A ft inhibits glutamatergic neurotransmission and reduces synaptic plasticity (Snyder et al., 2005). Treatment of cortical neuronal cultures with Aft facilitates endocytosis of NMDA receptor. Aft-mediated endo-cytosis of NMDA receptor requires the a-1 nicotinic receptor, protein phosphatase 2B, and the tyrosine phosphatase STEP. Dephosphorylation of the NMDA receptor subunit NR2B at Tyrl472 correlates with receptor endocytosis. The addition of a y-secretase inhibitor not only reduces Aft but also restores surface expression of NMDA receptors, suggesting that A plays an important role in the regulation of NMDA and AMPA receptor trafficking (Snyder et al., 2005 Morishita et al., 2005). 

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