Modulation of intercellular calcium signaling in astrocytes by extracellular calcium and magnesium

The extracellular concentrations of Ca2+ and Mg2+ are well known to play important roles in the function of the central nervous system. We examined the effects of extracellular Ca2+ and Mg2+ on ATP release and intercellular signaling in astrocytes. The extent of propagation of intercellular Ca2+ waves evoked by mechanical stimulation was increased by reduction of extracellular Ca2+ ([Ca2+](o)) or Mg2+ concentration ([Mg2+](o)) and was decreased by elevated [Mg2+](o). Reduction of extracellular Ca2+ concentration ([Ca2+](o)) evokes intercellular Ca2+ signaling in astrocytes; a similar effect was observed in response to change from 5 mM [Mg2+](o) to 0 [Mg2+](o). Release of low-molecular-weight dyes and ATP was also activated by low [Ca2+](o) or [Mg2+](o) and inhibited by high [Ca2+](o) or [Mg2+](o). Astrocytes showed low [Ca2+](o)-activated whole cell currents consistent with currents through connexin hemichannels. These currents were inhibited by extracellular Mg2+. We conclude that extracellular divalent cations modulate intercellular Ca2+ signaling in astrocytes by modulating the release of ATP, possibly via connexin hemichannels. (C) 2003 Wiley-Liss, Inc.