Glial Calcium: Homeostasis and Signaling Function

Verkhratsky, Alexej, Richard K. Orkand, and Helmut Kettenmann. Glial Calcium: Homeostasis and Signaling Function. Physiol. Rev. 78: 99–141, 1998. — Glial cells respond to various electrical, mechanical, and chemical stimuli, including neurotransmitters, neuromodulators, and hormones, with an increase in intracellular Ca 2+ concentration ([Ca 2+ ] i ). The increases exhibit a variety of temporal and spatial patterns. These [Ca 2+ ] i responses result from the coordinated activity of a number of molecular cascades responsible for Ca 2+ movement into or out of the cytoplasm either by way of the extracellular space or intracellular stores. Transplasmalemmal Ca 2+ movements may be controlled by several types of voltage- and ligand-gated Ca 2+ -permeable channels as well as Ca 2+ pumps and a Na + /Ca 2+ exchanger. In addition, glial cells express various metabotropic receptors coupled to intracellular Ca 2+ stores through the intracellular messenger inositol 1,4,5-trisphosphate. The interplay of different molecular cascades enables the development of agonist-specific patterns of Ca 2+ responses. Such agonist specificity may provide a means for intracellular and intercellular information coding. Calcium signals can traverse gap junctions between glial cells without decrement. These waves can serve as a substrate for integration of glial activity. By controlling gap junction conductance, Ca 2+ waves may define the limits of functional glial networks. Neuronal activity can trigger [Ca 2+ ] i signals in apposed glial cells, and moreover, there is some evidence that glial [Ca 2+ ] i waves can affect neurons. Glial Ca 2+ signaling can be regarded as a form of glial excitability.