A Specific and Essential Role for Na,K-ATPase alpha 3 in Neurons Co-expressing alpha 1 and alpha 3
2013 (English)In: Journal of Biological Chemistry, ISSN 0021-9258, E-ISSN 1083-351X, Vol. 288, no 4, 2734-2743 p.Article in journal (Refereed) Published
Most neurons co-express two catalytic isoforms of Na,K-ATPase, the ubiquitous alpha 1, and the more selectively expressed alpha 3. Although neurological syndromes are associated with alpha 3 mutations, the specific role of this isoform is not completely understood. Here, we used electrophysiological and Na+ imaging techniques to study the role of alpha 3 in central nervous system neurons expressing both isoforms. Under basal conditions, selective inhibition of alpha 3 using a low concentration of the cardiac glycoside, ouabain, resulted in a modest increase in intracellular Na+ concentration ([Na+](i)) accompanied by membrane potential depolarization. When neurons were challenged with a large rapid increase in [Na+](i), similar to what could be expected following suprathreshold neuronal activity, selective inhibition of alpha 3 almost completely abolished the capacity to restore [Na+](i) in soma and dendrite. Recordings of Na, K-ATPase specific current supported the notion that when [Na+](i) is elevated in the neuron, alpha 3 is the predominant isoform responsible for rapid extrusion of Na+. Low concentrations of ouabain were also found to disrupt cortical network oscillations, providing further support for the importance of alpha 3 function in the central nervous system. The alpha isoforms express a well conserved protein kinase A consensus site, which is structurally associated with an Na+ binding site. Following activation of protein kinase A, both the alpha 3-dependent current and restoration of dendritic [Na+](i) were significantly attenuated, indicating that alpha 3 is a target for phosphorylation and may participate in short term regulation of neuronal function.
Place, publisher, year, edition, pages
2013. Vol. 288, no 4, 2734-2743 p.
Basal conditions, Central nervous systems, Conserved proteins, Cortical network, Isoforms, Low concentrations, Membrane potentials, Neuronal activities, Neuronal function, Protein kinase A, Rapid extrusion, Selective inhibition, Short-term regulation, Suprathreshold
Biochemistry and Molecular Biology
IdentifiersURN: urn:nbn:se:kth:diva-119049DOI: 10.1074/jbc.M112.425785ISI: 000314211500057PubMedID: 23195960ScopusID: 2-s2.0-84873828994OAI: oai:DiVA.org:kth-119049DiVA: diva2:609908
FunderSwedish Research CouncilScience for Life Laboratory - a national resource center for high-throughput molecular bioscience
QC 201303082013-03-082013-03-052013-08-29Bibliographically approved