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A specific and essential role for Na,K‐ATPase α3 in neurons co‐expressing α1 and α3
Author(s) -
Kruusmägi Markus,
Azarias Guillaume,
Connor Siobhan,
Akkuratov Evgeny E,
Brismar Hjalmar,
Broberger Christian,
Aperia Anita
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.726.7
Subject(s) - gene isoform , ouabain , depolarization , sodium channel , chemistry , phosphorylation , microbiology and biotechnology , intracellular , sodium , membrane potential , biophysics , neuroscience , biochemistry , biology , gene , organic chemistry
Most neurons co‐express two catalytic isoforms of Na,K‐ATPase, the ubiquitous α1, and the more selectively expressed α3. Although neurological syndromes are associated with α3 mutations, the specific role of this isoform is not completely understood. Here we used electrophysiology and sodium imaging to study the role of α3 in neurons expressing both isoforms. Under basal conditions, selective inhibition of α3 using a low concentration of the cardiac glycoside ouabain resulted in a modest increase in the intracellular sodium 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, inhibition of α3 almost completely abolished the capacity to restore [Na + ] i in dendrites. Recordings of Na,K‐ATPase‐specific current supported the notion that α3 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 α3 function in the central nervous system. The α isoforms express a well conserved protein kinase A (PKA) consensus site, which is structurally associated with a Na + binding site. Activation of PKA significantly attenuated both the α3 dependent current and restoration of dendritic [Na + ] i , indicating that α3 is a target for phosphorylation and may participate in short‐term regulation of neuronal function.