Ionic mechanisms in glutamate-induced astrocyte swelling: Role of K⁺ influx

L-Glutamate (L-GLU) induced astrocyte swelling in a time- and concentration-dependent, as well as Na⁺and Ca²⁺-dependent, and Cl^- independent manner. Swelling was prevented by MK-801, cystine, and ouabain. Since L-GLU swelling is ionically dependent, we determined the role of various ions in such swelling. Our results indicate that K⁺ uptake plays a major role in the mechanism of L-GLU-induced astrocyte swelling. Like swelling, K⁺ uptake is dependent on Ca²⁺ and Na⁺, but not on Cl^-. Likewise, K⁺ uptake was inhibited by MK-801, cystine, and ouabain. The K⁺ channel blockers, Ba²⁺ and tetraethylammonium, partially prevented L-GLU- induced swelling. In addition to K⁺ channels, K⁺ influx may also be mediated through Na⁺/K⁺-ATPase, as its activity is increased by L-GLU uptake along with the required Na⁺. Taken together, the data suggest that K⁺ influx plays a key role in the mechanism of L-GLU-mediated astrocyte swelling.