Molecular aspects of glutamate receptors and sodium-calcium exchange carriers in mammalian brain: implications for neuronal development and degeneration.

Abstract

N-Methyl-D-aspartate (NMDA) and L-glutamate activate membrane receptors that produce substantial permeation of Na+, K+ and Ca2+ through the neuronal membrane. These ionic fluxes are intimately linked to processes that regulate neuronal survival, growth and differentiation. Intracellular free Ca2+ concentrations are thought to be particularly important determinants of the vulnerability of neurons to excessive excitatory stimulation produced through activation of NMDA receptors. In order to understand the molecular events involved in both NMDA receptor activation and regulation of intracellular Ca2+ levels, we have purified and reconstituted the protein complexes that form the NMDA/glutamate receptors in rat brain synaptic membranes and those that constitute the Na(+)-Ca2+ antiporters in bovine brain synaptic membrane. The molecular properties of these protein complexes are described, and information from the most recent studies of exploration of the molecular structures of these receptors and transport carriers is summarized.