Glutamate release through connexin 43 by cultured astrocytes in a stimulated hypertonicity model

Abstract We investigated the role of connexin 43 (Cx43) hemichannels in the release of glutamate by astrocytes after hypertonic stimulus. Mechanical, osmotic and oxidative stress, and changes in the extracellular or intracellular Ca 2+ levels induce connexin hemichannels located in the plasma membrane to open and release small ions and molecules with signaling potential such as glutamate, ATP, etc. In our past studies, we primarily found that acute hypertonic stimulus induced the release of glutamate. Since glutamate release was involved with several routes, we studied its release routes by astrocytes incubated in a hypertonic media for various periods. The glutamate release was increased after hypertonic stimulus. Glutamate release in hypertonic stimulus was inhibited by gap junction or Cx43 hemichannel blockers, but not by antagonists of purinergic receptor (P2XnR), glutamate transport inhibitors, intracellular Ca 2+ blockers, and pannexin 1(Panx1) hemichannel. The results suggest that glutamate release by the Cx43 hemichannels is likely to feature in the response of cultured astrocytes to hypertonic stimulus.