Document Type


Degree Name

Master of Science (MSc)




Faculty of Science

First Advisor

Dr. Lillian DeBruin

Advisor Role



Sodium-potassium adenosine triphosphatase (Na+/K+-ATPase) is an integral membrane protein with known involvement in the maintenance of resting membrane potentials, nutrient uptake, cellular signal transduction, and cell-cell adhesion. The functional enzyme contains a catalytic alpha subunit and a glycosylated beta subunit, of which three isoforms of each are known to exist in the central nervous system (CNS). Altered expression and/or activity of Na+/K+-ATPase subunit isoforms has been previously implicated in the pathophysiology of several neurological disorders. This study characterized Na+/K+-ATPase expression and distribution in the myelin membrane, identified its specific heterodimeric forms and binding partners, and explored its possible involvement in demyelinating disorders, such as multiple sclerosis. For the first time, Na+/K+-ATPase α1, α2, and α3, as well as the β1, β2, and β3 subunits, were shown to co-express within a tissue of the CNS. These six isoforms, in addition to six isozymes (α1β1, α2β1, α2β3, α3β1, α3β2, and α3β3), of Na+/K+-ATPase were identified in myelin isolated from mouse brain; this expression shared both similarities and differences with neurons, astrocytes and/or oligodendrocytes. The major isozymes of Na+/K+-ATPase identified in myelin were α1β1, α2β3, and α3β1. Co-immunoprecipitation (co-IP) assays demonstrated that the three alpha isoforms of Na+/K+-ATPase in the myelin sheath can interact with other Na+/K+-ATPase alpha and beta subunit isoforms, in addition to associating with certain myelin-specific proteins and other protein types. These protein binding partners of Na+/K+-ATPase have known cellular functions, including RNA splicing, involvement in cell-cell migration and adhesion, the mediation of cytoskeletal interactions, and the regulation of protein degradation and apoptosis; they also suggested localization of Na+/K+-ATPase to the adherens junctions, tight junctions, caveolin-1 enriched microdomains, lipid rafts and tetraspanin-enriched microdomains of myelin. Western blot analysis indicated that Na+/K+-ATPase expression varies over post-natal development. Distinct differences in protein expression were observed between healthy and diseased myelin. In particular, demyelinating ND4 mice exhibited severe impairment of Na+/K+-ATPase β1 subunit maturation. Overall, this study has provided a comprehensive look into Na+/K+-ATPase expression and interactions within the myelin sheath, emphasizing its importance to both myelin structure and function.

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