Functional Study of Glutamate Receptor Channels in Brain Slices

Glutamate is the major excitatory neurotransmitter in the central nervous system (CNS). Glutamate binds to and activates receptors coupled to both ligand-gated ion channels (ionotropic) and G proteins (metabotropic). The ionotropic glutamate receptors are permeable to cations, including Ca(2+), whereas metabotropic glutamate receptors can trigger the release of Ca(2+) from intracellular stores. Therefore the activation of glutamate receptors can increase cytoplasmic Ca(2+) levels, resulting in the activation of a variety of Ca(2+)-dependent processes. An increase in intracellular Ca(2+) in brain cells is potentially neurotoxic and has been linked to many neurodegenerative disorders and neuronal cell death. Antagonists of glutamate-receptor channels have previously been shown to reduce the neurotoxic damage in a variety of animal models of neurological disorders. Because of the link between glutamate receptors, Ca(2+) signaling, and neuronal death, elucidating the molecular mechanistic details of these processes will be crucial to understanding the pathology of various neurodegenerative diseases.