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

The extracellular concentrations of Ca 2+ and Mg 2+ are well known to play important roles in the function of the central nervous system. We examined the effects of extracellular Ca 2+ and Mg 2+ on ATP release and intercellular signaling in astrocytes. The extent of propagation of intercellular Ca 2+ waves evoked by mechanical stimulation was increased by reduction of extracellular Ca 2+ ([Ca 2+ ] o ) or Mg 2+ concentration ([Mg 2+ ] o ) and was decreased by elevated [Mg 2+ ] o . Reduction of extracellular Ca 2+ concentration ([Ca 2+ ] o ) evokes intercellular Ca 2+ signaling in astrocytes; a similar effect was observed in response to change from 5 mM [Mg 2+ ] o to 0 [Mg 2+ ] o . Release of low‐molecular‐weight dyes and ATP was also activated by low [Ca 2+ ] o or [Mg 2+ ] o and inhibited by high [Ca 2+ ] o or [Mg 2+ ] o . Astrocytes showed low [Ca 2+ ] o –activated whole cell currents consistent with currents through connexin hemichannels. These currents were inhibited by extracellular Mg 2+ . We conclude that extracellular divalent cations modulate intercellular Ca 2+ signaling in astrocytes by modulating the release of ATP, possibly via connexin hemichannels. © 2003 Wiley‐Liss, Inc.