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

Abstract

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.