Requirement of Glycogenolysis for Uptake of Increased Extracellular K+ in Astrocytes: Potential Implications for K+ Homeostasis and Glycogen Usage in ... View Full Text


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Article Info

DATE

2013-03

AUTHORS

Junnan Xu, Dan Song, Zhanxia Xue, Li Gu, Leif Hertz, Liang Peng

ABSTRACT

The importance of astrocytic K(+) uptake for extracellular K(+) ([K(+)](e)) clearance during neuronal stimulation or pathophysiological conditions is increasingly acknowledged. It occurs by preferential stimulation of the astrocytic Na(+),K(+)-ATPase, which has higher K(m) and V(max) values than its neuronal counterpart, at more highly increased [K(+)](e) with additional support of the cotransporter NKCC1. Triggered by a recent DiNuzzo et al. paper, we used administration of the glycogenolysis inhibitor DAB to primary cultures of mouse astrocytes to determine whether K(+) uptake required K(+)-stimulated glycogenolysis. KCl was increased by either 5 mM (stimulating only the Na(+),K(+)-ATPase) or 10 mM (stimulating both transporters) in glucose-containing saline media prepared to become iso-osmotic after the addition. DAB completely inhibited both uptakes, the Na(+),K(+)-ATPase-mediated by preventing Na(+) uptake for stimulation of its intracellular Na(+)-activated site, and the NKCC1-mediated uptake by inhibition of depolarization- and L-channel-mediated Ca(2+) uptake. Drugs inhibiting the signaling pathways involved in either of these processes also abolished K(+) uptake. Assuming similar in vivo characteristics, partly supported by literature data, K(+)-stimulated astrocytic K(+) uptake must discontinue after normalization of extracellular K(+). This will allow Kir1.4-mediated release and reuptake by the less powerful neuronal Na(+),K(+)-ATPase. More... »

PAGES

472-485

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1007/s11064-012-0938-3

    DOI

    http://dx.doi.org/10.1007/s11064-012-0938-3

    DIMENSIONS

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    PUBMED

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