Intracellular calcium release in central neurones

Abstract

Ca²⁺signalling in neurones is primarily fast, by influx through voltage- or ligand-gated channels in the surface membrane. The role and mechanisms of Ca release from intracellular stores in central neurones are not as well established as slow metabolic or secretory responses in peripheral tissues or in cardiac e–c coupling. Ca release in neurones produces short-term changes in excitability due to activation of Ca²⁺-gated channels, and less well defined long-term changes in excitability or synaptic strength. Neither mode of Ca release, via IP3 or CICR, is easily demonstrated physiologically in neurones and the role and mechanisms are reviewed with reference to peripheral tissues, morphological specializations and properties of intracellular Ca channels. It can be speculated that IP3 provides a diffusible signal that can produce Ca release in particular regions of the cell, near the nucleus for coupling to gene activation, in specific areas of the cytosol to modify structural proteins, and to activate Ca-dependent kinases, processes that might produce changes in excitability. Evidence of an inhibitory action of Ca²⁺influx on IP3 evoked release is presented. The role of CICR appears to be simply local amplification of membrane Ca signals, originating with Ca influx during action potentials, Ca-permeable ligand-gated channels and possibly also with IP3 evoked release. Because of the restricted diffusion of Ca ions, the amplification may depend on local structural specializations.