Potassium channel activity and glutamate uptake are impaired in astrocytes of seizure-susceptible DBA/2 mice

Authors: Inyushin, Mikhail; Kucheryavykh, Lilia Y.; Kucheryavykh, Yuriy V.; Nichols, Colin G.¹; Buono, Russell J.²; Ferraro, Thomas N.³; Skatchkov, Serguei N.; Eaton, Misty J.⁴

Source: Epilepsia, Volume 51, Number 9, September 2010 , pp. 1707-1713(7)

Publisher: Wiley-Blackwell

Abstract:

Summary Purpose: 

KCNJ10 encodes subunits of inward rectifying potassium (Kir) channel Kir4.1 found predominantly in glial cells within the brain. Genetic inactivation of these channels in glia impairs extracellular K⁺ and glutamate clearance and produces a seizure phenotype. In both mice and humans, polymorphisms and mutations in the KCNJ10 gene have been associated with seizure susceptibility. The purpose of the present study was to determine whether there are differences in Kir channel activity and potassium- and glutamate-buffering capabilities between astrocytes from seizure resistant C57BL/6 (B6) and seizure susceptible DBA/2 (D2) mice that are consistent with an altered K⁺ channel activity as a result of genetic polymorphism of KCNJ10. Methods: 

Using cultured astrocytes and hippocampal brain slices together with whole-cell patch-clamp, we determined the electrophysiologic properties, particularly K⁺ conductances, of B6 and D2 mouse astrocytes. Using a colorimetric assay, we determined glutamate clearance capacity by B6 and D2 astrocytes. Results: 

Barium-sensitive Kir currents elicited from B6 astrocytes are substantially larger than those elicited from D2 astrocytes. In addition, potassium and glutamate buffering by D2 cortical astrocytes is impaired, relative to buffering by B6 astrocytes. Discussion: 

In summary, the activity of Kir4.1 channels differs between seizure-susceptible D2 and seizure-resistant B6 mice. Reduced activity of Kir4.1 channels in astrocytes of D2 mice is associated with deficits in potassium and glutamate buffering. These deficits may, in part, explain the relatively low seizure threshold of D2 mice.

Keywords: Astrocyte; Seizure; Potassium buffering; Glutamate clearance; Kir4.1

Document Type: Research article

DOI: http://dx.doi.org/10.1111/j.1528-1167.2010.02592.x

Affiliations: 1: Department of Cell Biology, Washington University School of Medicine, St. Louis, Missouri, U.S.A. 2: Department of Research and Development, Veterans Affairs Medical Center, Coatesville, Pennsylvania, U.S.A. 3: Department of Psychiatry, University of Pennsylvania, Philadelphia, Pennsylvania, U.S.A. 4: Biochemistry, Universidad Central del Caribe, School of Medicine, Bayamón, Puerto Rico, U.S.A.

Publication date: 2010-09-01

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