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.