Glial Ca2 signalling endoplasmic reticulum takes the leading role

Glial cells have all the components of Ca2+ homeostatic/signalling machinery discussed above. An important difference between glial cells and neurones, however, is the relative scarcity of voltage-gated Ca2+ channels in glial cells. The majority of mature astrocytes, oligodendrocytes and Schwann cells do not express voltage-gated Ca2+ channels. Nonetheless, voltage-gated Ca2+ currents are present in immature astroglial cells and oligodendrocyte precursors, and their expression is down-regulated during development. It is likely that voltage-gated Ca2+ channels are involved in growth and differentiation of glial cells.

Ca2+ entry pathways in mature glial cells are represented by several types of Ca2+ permeable ligand-gated channels (most notably by ionotropic glutamate and P2X purinoreceptors) and store-operated Ca2+ channels.

The main source for glial Ca2+ signalling is associated with the ER Ca2+ store. The intra-ER Ca2+ concentration in glial cells varies between 100-300 ^M, thus being lower compared to neurones (where intra-ER free Ca2+ reaches 300-800 ^M). All types of glial cells express numerous metabotropic receptors and their activation causes an increase in cytosolic concentration of InsP3, which binds to the InsP3Rs and causes rapid Ca2+ release. It seems that InsP3-induced Ca2+ release represents the leading mechanism of Ca2+ signalling in glia. Although both astrocytes and microglia express RyRs, they play a relatively minor (if any) role in shaping Ca2+ signals in these cells. The RyRs are more important in OPCs and immature oligodendrocytes, where they are directly coupled to voltage-gated Ca2+ channels located in the plasma membrane along processes. Thus, opening of voltage-gated Ca2+ channels activates RyRs and triggers depolarization-induced Ca2+ release, providing a potential mechanism by which axonal electrical activity may regulate oligodendroglial Ca2+ signals and process outgrowth.

The release of Ca2+ from intracellular stores lowers intra-ER Ca2+ concentration, which in turn triggers opening of SOCC, which are abundantly present in all types of glial cells. Although the molecular nature of these channels and details of their activation mechanism are unknown, they are functionally very important, as their activation produces prolonged Ca2+ signals, which may significantly outlast the duration of stimulation.

The interplay between Ca2+ release, Ca2+ reuptake into the ER and SOCC-related Ca2+ entry determines the shape of the resulting Ca2+ signal, which may vary from a rapid and transient peak-like response, through [Ca2+]j elevations lasting up to hundreds of seconds with a clear plateau, to multiple transient Ca2+ oscillations. These kinetically different [Ca2+] changes underlie the temporal coding of the Ca2+ signal, whereas [Ca2+]i oscillations are responsible for frequency coding of the Ca2+ signal.

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