Cardiac glycosides ouabain and digoxin interfere with the regulation of glutamate transporter GLAST in astrocytes cultured from neonatal rat brain

Nguyen, K, Buljan, V, Else, P, Pow, D and Balcar, V 2010, 'Cardiac glycosides ouabain and digoxin interfere with the regulation of glutamate transporter GLAST in astrocytes cultured from neonatal rat brain', Neurochemical Research, vol. 35, no. 12, pp. 2062-2069.


Document type: Journal Article
Collection: Journal Articles

Title Cardiac glycosides ouabain and digoxin interfere with the regulation of glutamate transporter GLAST in astrocytes cultured from neonatal rat brain
Author(s) Nguyen, K
Buljan, V
Else, P
Pow, D
Balcar, V
Year 2010
Journal name Neurochemical Research
Volume number 35
Issue number 12
Start page 2062
End page 2069
Total pages 8
Publisher Springer
Abstract 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 ?M). 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
Subject Cell Neurochemistry
Keyword(s) Cultured astrocytes
D-aspartate
Digoxin
Glutamate transporter GLAST
Na+/K+-ATPase
Ouabain
Rottlerin
DOI - identifier 10.1007/s11064-010-0274-4
Copyright notice © 2010 The Author(s)
ISSN 0364-3190
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