Glutamate‐induced calcium signaling in astrocytes

Abstract

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.