Coding of neuronal differentiation by calcium transients

Abstract

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.

Overexpression of an α1H (Cav3.2) T-type Calcium Channel during Neuroendocrine Differentiation of Human Prostate Cancer Cells

“…Such window currents occurring through T-type calcium channels have been reported in other cells (26,29,38). This slight increase in cytosolic calcium concentration may serve in facilitating neurite growth, as proposed in nerve cells (15). Furthermore, it is now well established that calcium homeostasis mechanisms are involved in the control of cell death (39).…”

“…Calcium entry through voltage-gated calcium channels is reported to be involved in differentiation and neurite outgrowth in other cells (12)(13)(14)(15). It has been shown, for example, in the pheochromocytoma cell line (PC12 cells) that neuroendocrine differentiation is accompanied by an increased expression of voltage-dependent channels like low-voltage activated (LVA) (12) and high-voltage activated (HVA) calcium channels (14,16).…”

Neuronal Activity Regulates Correlated Network Properties of Spontaneous Calcium Transients in AstrocytesIn Situ

“…Thus, the finding that reactive astrocytes lack [Ca 2ϩ ] i transients not only demonstrates that spontaneous astrocytic activity depends on the functional state of these cells, but indicates a relationship with the regulation of neural transmission. Because changes in [Ca 2ϩ ] i control gene expression and cell differentiation (Spitzer et al, 2000), the lack of spontaneous [Ca 2ϩ ] i transients in astrocytes might contribute to the activation of astrocytes. Taken together, the above data show that spontaneous [Ca 2ϩ ] i oscillations are a common property of most brain astrocytes that is lost when they become activated after injury.…”

“…It is essential for neuronal migration, axonal and dendritic growth, and the formation and refinement of neural connections and synapses (Katz and Shatz, 1996;Komuro and Rakic, 1998;Feller, 1999;Spitzer et al, 2000;Stellwagen and Shatz, 2002). Changes and oscillations in intracellular Ca 2ϩ concentrations ([Ca 2ϩ ] i ) are the main mechanism by which spontaneous activity controls neural development (Berridge, 1998).…”

GABA-mediated giant depolarizing potentials as coincidence detectors for enhancing synaptic efficacy in the developing hippocampus

“…The depolarizing action of GABA during GDPs results in calcium influx through the activation of Nmethyl-D-aspartate (NMDA) receptors and voltage-dependent calcium channels (11)(12)(13). Thus, as in many others developing systems (14)(15)(16)(17), GDPs ensure large calcium oscillations even in neurons with few synapses (6, 13).…”