Excitatory amino acid receptors, second messengers and regulation of intracellular Ca2+ in mammalian neurons.

As we have learnt from earlier articles in our series on the pharmacology of excitatory amino acids, neurons and glia express several subtypes of excitatory amino acid receptor, the activation of which increases intracellular free calcium ion concentration. In this sixth article, Mark Mayer and Richard Miller detail the mechanisms and consequences of this activity. Ionotropic excitatory amino acid receptors, most notably those activated by NMDA, allow Ca2+ influx as a result of passive diffusion down its concentration gradient. Metabotropic receptors trigger an increase in polyphosphoinositide metabolism, and release of Ca2+ from intracellular stores. The increase in [Ca2+]i mediated by excitatory amino acids underlies a complex cellular physiology, including the activation of other second messenger systems, and contributes to the initiation of long-term potentiation.