Glutamate-induced calcium signaling in astrocytes

Astrocytes respond to the excitatory neurotransmitter glutamate with dynamic spatio-temporal changes in intracellular calcium [Ca2+]i. Although they share a common wave-like appearance, the different [Ca2+]i changes--an initial spike, sustained elevation, oscillatory intracellular waves, and regenerative intercellular waves--are actually separate and distinct phenomena. These separate components of the astrocytic Ca2+ response appear to be generated by two different signal transduction pathways. The metabotropic response evokes an initial spatial Ca2+ spike that can propagate rapidly from cell to cell and appears to involve IP3. The metabotropic response can also produce oscillatory intracellular waves of various amplitudes and frequencies that propagate within cells and are sustained only in the presence of external Ca2+. The ionotropic response, however, evokes a sustained elevation in [Ca2+]i associated with receptor-mediated Na+ and Ca2+ influx, depolarization, and voltage-dependent Ca2+ influx. In addition, the ionotropic response can lead to regenerative intercellular waves that propagate smoothly and nondecrementally from cell to cell, possibly involving Na+/Ca2+ exchange. All these astrocytic [Ca2+]i changes tend to appear wave-like, traveling from region to region as a transient rise in [Ca2+]i. Nevertheless, as our understanding of the cellular events that underlie these [Ca2+]i changes grows, it becomes increasingly clear that glutamate-induced Ca2+ signaling is a composite of separate and distinct phenomena, which may be distinguished not based on appearance alone, but rather on their underlying mechanisms.