Coding of neuronal differentiation by calcium transients

Excitability has long been recognized as the basis for rapid signaling in the mature nervous system, but roles of channels and receptors in controlling slower processes of differentiation have been identified only more recently. Voltage-dependent and transmitter-activated channels are often expressed at early stages of development prior to synaptogenesis, and allow influx of Ca(2+). Here we examine the functions of spontaneous transient elevations of intracellular Ca(2+) in embryonic neurons. These Ca(2+) transients abruptly raise levels of Ca(2+) as much as tenfold, for brief periods, repeatedly, and can be highly localized. Like cloudbursts on the developing landscape, Ca(2+) transients modulate growth and stimulate differentiation, in a frequency-dependent manner, probably by changes in phosphorylation or proteolysis of regulatory and structural proteins in local regions. We review the mechanisms by which Ca(2+) transients are generated and their effects in regulating motility via the cytoskeleton and differentiation via transcription.