Volume-sensitive chloride channels blocked by neuroprotective drugs in human glial cells (U-138MG)

Glial cell swelling in hypotonic media activates an anionic channel that was found previously to be permeable to amino acids. It is possible that the same channel is also activated when glial cells swell in pathologic conditions, like ischemia or hypoxia, and it could be partly responsible for the release of glutamate appearing in such conditions. Many drugs have been developed to block glutamate release during ischemia. Six of these drugs were tested on human glial cells (U-138MG) in vitro to determine if they could block the swelling-activated anionic channels. Three of them, phenytoin, lidocaine, and flunarizine, had no effect. The other three could block the anionic channels: riluzole, nizofenone, and BW1003C87. Such blocking was reversible and the half inhibition concentration (IC50) of each of these drugs was within that observed for their inhibition of glutamate release by various authors. An important advantage of these three drugs is their capacity to inhibit glutamate release after the beginning of ischemia. It is concluded that the volume-sensitive anionic channel could be partly responsible for glutamate release during a cerebral ischemia.