Ionotropic glutamate receptors modeling

Taverna, F. A., Wang, L. Y., MacDonald, J. F., and Hampson, D. R. (1994). A transmembrane model for an ionotropic glutamate receptor predicted on the basis of the location of asparagine-linked oligosaccharides./. Biol. Chem. 269, 14159-14164. 

Ionotropic glutamate receptors also promote perturbations in ionic homeostasis that play a critical role in cerebral ischemia. For example, L, P/Q, and N-type calcium channel receptors mediate excessive calcium influx, and Ca " channel antagonists reduce ischemic brain injury in preclinical studies [12-14]. Zinc is stored in vesicles of excitatory neurons and coreleased upon depolarization after focal cerebral ischemia, resulting in neuronal death [15, 16]. Recently, imbalances in potassium have also been implicated in ischemic cell death. Compounds that selectively modulate a class of calcium-sensitive high conduc-tance potassium (maxi-K) channels protect brain against stroke in animal models [17]. 

Petri S, Kiaei M, Damiano M, Hiller A, WiUe E, Manfredi G, CaUngasan NY, Szeto HH, Beal MF (2006) CeU-permeable peptide antioxidants as a novel therapeutic approach in a mouse model of amyotrophic lateral sclerosis. J Neurochem 98 1141-1148 Planells-Cases R, Lerma J, Ferrer-Montiel A (2006) Pharmacological intervention at ionotropic glutamate receptor complexes. Curr Pharm Des 12 3583-3596 Postina R (2008) A closer look at alpha-secretase. Curr Alzheimer Res 5 179-186 Price JL, Morris JC (1999) Tangles and plaques in nondemented aging and preclinical Alzheimer s disease. Ann Neurol 45 358-368... 

Unfortunately, the impact of anticonvulsants on NA-induced seizures has not been modeled in this way. Given that many coxmtermeasures have different ligand receptor interactions, such an approach would need to be expanded to the other excitatory and inhibitory neurotransmitters and their respective receptors, which are involved in seizure induction and sustainment. However, validation of such an approach, using components of gross EEG recordings, may not be plausible because of the large number of ionotropic channels represented. An endpoint such as sustained elevated glutamate may be more appropriate. 

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