Na+, K+-ATPase: Ubiquitous Multifunctional Transmembrane Protein and its Relevance to Various Pathophysiological Conditions

Abstract

The Na+, K+-ATPase (NKA) is an ubiquitous enzyme consisting of α, β and γ subunits, and is responsible for the creation and maintenance of the Na+ and K+ gradients across the cell membrane by transporting 3 Na+ out and 2 K+ into the cell. Sodium pump regulation is tissue as well as isoform specific. Intracellular messengers differentially regulate the activity of the individual NKA isozymes. Regulation of specific NKA isozymes gives cells the ability to precisely coordinate NKA activity to their physiological requirements. It is the only known receptor for the cardiac glycosides used to treat congestive heart failure and cardiac arrhythmias. Endogenous ligands structurally similar to cardiac glycosides may act as natural regulators of the sodium pump in heart and other tissues. Identification of naturally occurring regulators of NKA could initiate the discovery of new hormone-like control systems involved in the etiology of selected disease processes, hence the importance of understanding the relation of the sodium pump and its ligands to disease. Diabetes has a marked effect on the metabolism of a variety of tissues and because the NKA is critical for the membrane potential and many transports, a change in its activity in diabetes would have profound consequence in these tissues. NKA is also involved in hypertension, salt balance, cardiovascular and renal disorders, sperm capacitation, cell volume regulation, apoptosis, rheumatoid arthritis, sepsis, neurological disorders, lung edema clearance and preeclampsia. NKA activity and expression in the collecting duct of kidney are modulated physiologically by hormones like aldosterone, vasopressin, and insulin. NKA enzyme activity and subunit levels are reduced in carcinoma, NKA-β levels were highly reduced in an invasive form of human renal clear cell carcinoma, androgen-dependent prostate cancer, in early stages of urothelial cancer, as well as in poorly differentiated, highly motile carcinoma cell lines obtained from various tissues suggesting a functional link between reduced NKA-β expression and cancer progression. It could be a target for the development of anticancer drugs as it serves as a signal transducer, it is a player in cell adhesion and its aberrant expression and activity are implicated in the development and progression of different cancers.KeywordsNa+, K+-ATPase (NKA); Cardiotonic steroids (CTS); Diabetes; Hypertension; Cardiovascular and renal disorders; Signal transducer; Anticancer drugs

Inhomogeneity Based Characterization of Distribution Patterns on the Plasma Membrane

“…We used the sodium-potassium pump (Na + /K + ATPase) [43] (Fig 3A and 3B), the transferrin receptor (TfR) [44] (Fig 3C and 3D), and caveolin1 (Cav1) [45] (Fig 3E and 3F). The Na + /K + ATPase is an integral membrane protein that is randomly distributed across the cell surface.…”

Investigating potentially salvageable penumbra tissue in an in vivo model of transient ischemic stroke using sodium, diffusion, and perfusion magnetic resonance imaging

“…swelling) [13, 18] and if energy deprivation persists this will ultimately lead to cell death [23, 24]. Most living cells have a high concentration of intracellular potassium and a low concentration of intracellular sodium [25]. During the early hours of ischemic stroke cytotoxic cerebral edema occurs in the presence of an intact blood brain barrier (BBB).…”

RNAi Validation of Pancreatic Cancer Antigens Identified by Cell Surface Proteomics

“…A number of studies, including studies performed on ovarian, colon, and pancreatic cancer, have correlated Integrin αvβ6 expression with progression into advance stages of disease [59][60][61]. Na + /K + ATPase is a family of isoenzymes that are found on the plasma membrane that catalyzes the efflux of cytoplasmic Na + and uptake of extracellular K + [62]. The isoenzyme consists of alpha subunits, beta subunits, and FXYD proteins.…”