Cardiac Glycosides Ouabain and Digoxin Interfere with the Regulation of Glutamate Transporter GLAST in Astrocytes Cultured from Neonatal Rat Brain

• Published in: Neurochemical research 2010-12, Vol.35 (12), p.2062-2069
• Main Authors: Nguyen, Khoa T. D., Buljan, Vlado, Else, Paul L., Pow, David V., Balcar, Vladimir J.
• Format: Article
• Language: English
• Subjects: Animals; Animals, Newborn; Astrocytes - drug effects; Astrocytes - enzymology; Astrocytes - metabolism; Biochemistry; Biomedical and Life Sciences; Biomedicine; Brain - cytology; Brain - drug effects; Brain - enzymology; Brain - metabolism; Cell Biology; Digoxin - pharmacology; Excitatory Amino Acid Transporter 1 - metabolism; Immunohistochemistry; Neurochemistry; Neurology; Neurosciences; Original Paper; Ouabain - pharmacology; Rats; Rats, Sprague-Dawley; Sodium-Potassium-Exchanging ATPase - metabolism
• ISSN: 0364-3190; 1573-6903
• DOI: 10.1007/s11064-010-0274-4

Glutamate transport (GluT) in brain is mediated chiefly by two transporters GLT and GLAST, both driven by ionic gradients generated by (Na + , K + )-dependent ATPase (Na + /K + -ATPase). GLAST is located in astrocytes and its function is regulated by translocations from cytoplasm to plasma membrane in the presence of GluT substrates. The phenomenon is blocked by a naturally occurring toxin rottlerin. We have recently suggested that rottlerin acts by inhibiting Na + /K + -ATPase. We now report that Na + /K + -ATPase inhibitors digoxin and ouabain also blocked the redistribution of GLAST in cultured astrocytes, however, neither of the compounds caused detectable inhibition of ATPase activity in cell-free astrocyte homogenates (rottlerin inhibited app. 80% of Pi production from ATP in the astrocyte homogenates, IC50 = 25 μM). Therefore, while we may not have established a direct link between GLAST regulation and Na + /K + -ATPase activity we have shown that both ouabain and digoxin can interfere with GluT transport and therefore should be considered potentially neurotoxic.