Calcium Channel Signaling in Astrocytes

Abstract

It has been known for more than a century that the brain contains not only neurons but also non-neuronal cells. Most of the non-neuronal cells belong to the two glial cell types, oligodendrocytes and astrocytes. In many species, including man, they vastly outnumber neurons (1). At the beginning of this century several attempts were made to study the role(s) of glial cells. Many theories were suggested but little solid evidence was obtained, leading Ramon and Cajal (2) to the visionary conclusion that the functions of glial cells were unknown and would remain so for a long time to come, because no methodologies were available to study these functions. With the remarkable development in electrophysiological techniques during the following decades, neuronal characteristics were elucidated in ever greater detail, whereas the possibility of a major role of glial cells in brain function was more or less disregarded. This situation began to change in the 1950s. With the aid of histological techniques it was shown that oligodendrocytes synthesize myelin and that radial glial cells (immature astrocytes) serve a guiding role during neuronal migration. Purified samples of either neurons or glial cells were first obtained by Hyden (3), using microdissection; subsequently, neurons and different types of glial cells were prepared by centrifugation or culturing techniques. Another development of decisive importance for the interest in glial cell studies was the development of microelectrodes which made it possible to demonstrate huge alterations in extracellular concentrations of cations (primarily potassium and calcium) during both normal function of the CNS and pathological states, e.g., seizures, hypoglycemia, and ischemia. This new knowledge paved the way for the concept that neurons and astrocytes share a common extracellular space, sheltered behind the bloodbrain barrier and, in conjunction, regulate the local concentration of neuroactive compounds like potassium ions and glutamate. Finally, the development of patch-clamp techniques to study ion channels and of imaging techniques to determine intracellular concentrations (activities) of calcium (4) and, more recently, of sodium and potassium in visually selected individual cells and/or microareas of cells, are as well suited to measure characteristics of glial cells as of neutrons.