Na,K-ATPase Subunit Heterogeneity as a Mechanism for Tissue-Specific Ion Regulation

Subunit Isoform Selectivity in Assembly of Na,K-ATPase α-β Heterodimers

“…However, selective co-immunoprecipitation of the ␣ 2 subunit but not of the ubiquitously expressed ␣ 1 subunit, with the ␤ 2 subunit from mouse and rat brain (19,26), as well as from heart and adrenal medullary cells of guinea pigs and rats (26,27) suggest that the ␣ 2 subunit is the preferred binding partner of the ␤ 2 subunit. In support of this hypothesis, the tissue expres-sion pattern of the ␤ 2 subunit, mainly in muscle and nervous system, is similar to that of the ␣ 2 subunit (3,7).…”

“…However, very little is known about particular ␣-␤ heterodimers responsible for these roles. Transfection studies indicate that each of the four ␣ subunit isoforms can assemble with each of the three ␤ subunit isoforms and form a functional pump (6,7,25). These data imply that in cells co-expressing multiple Na,K-ATPase subunits isoforms, various ␣ and ␤ isoforms also assemble in different combinations, dependent on their relative cellular content.…”

“…The ␣ 2 isoform is expressed mainly in muscle and nervous system (1-3, 6, 7); the ␣ 3 isoform is expressed mainly in neurons (8,9), whereas the ␣ 4 isoform is found only in testis (10,11). The ␤ 2 isoform is expressed predominantly in brain and muscle (3,7), whereas the ␤ 3 isoform is mainly expressed in lung, testis, skeletal muscle, and liver (12,13). The ␣ 2 isoform regulates contractility of cardiac, smooth, and skeletal muscle and plays a key role in the modulation of blood pressure in response to stress (3,14,15).…”

Distribution of the Na,K-ATPase α Subunit in the Rat Spiral Ganglion and Organ of Corti

“…Mechanisms to maintain hyperpolarized membrane potentials and restore intracellular concentration gradients are essential for excitable cells and vary depending on their particular physiology (Blanco 2005). The Na,KATPase (NKA) is a membrane-bound protein that uses energy from the hydrolysis of adenosine triphosphate (ATP) to extrude three sodium ions for every two potassium ions taken into the cell.…”

α3Na+/K+-ATPase Deficiency Causes Brain Ventricle Dilation and Abrupt Embryonic Motility in Zebrafish

“…regulation of cell volume, pH, Na ϩ -coupled secondary transport of molecules and neurotransmitters, and the excitability of muscle and neuronal cells (1,2). In mammals, the four ␣ (␣ 1 , ␣ 2 , ␣ 3 , and ␣ 4 ) isoforms display distinct tissue-specific expression patterns (2,3).…”