Identification of a pool of non-pumping Na/K-ATPase.
Recent studies have ascribed many non-pumping functions to the Na/K-ATPase. Here, we present experimental evidence demonstrating that over half of the plasma membrane Na/K-ATPase in LLC-PK1 cells is performing cellular functions other than ion pumping. This "non-pumping" pool of Na/K-ATPase, like the pumping pump, binds ouabain. Depletion of either cholesterol or caveolin-1 moves some of the "non-pumping" Na/K-ATPase into the pumping pool. Graded knock-down of the alpha1 subunit of the Na/K-ATPase eventually results in loss of this "non-pumping" pool while preserving the pumping pool. Our prior studies indicate that a loss of the non-pumping pool is associated with a loss of receptor function as evidenced by the failure of ouabain administration to induce the activation of Src and/or ERK. Therefore, our new findings suggest that a substantial amount of surface-expressed Na/K-ATPase, at least in some types of cells, may function as non-canonical ouabain-binding receptors.
Liang
Man
M
Department of Physiology, Pharmacology, Metabolism, and Cardiovascular Sciences, University of Toledo Health Science Campus, Toledo, Ohio 43614, USA.
Tian
Jiang
J
Liu
Lijun
L
Pierre
Sandrine
S
Liu
Jiang
J
Shapiro
Joseph
J
Xie
Zi-Jian
ZJ
D000818:Animals; D051242:Caveolin 1 / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D002462:Cell Membrane / Q000235:genetics / Q000378:metabolism*; D004789:Enzyme Activation / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006801:Humans; D010042:Ouabain / Q000494:pharmacology; D021122:Protein Subunits / Q000172:deficiency / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000235:genetics / Q000378:metabolism*; D019061:src-Family Kinases / Q000378:metabolism
D051242:Caveolin 1; D021122:Protein Subunits; C028996:cardiac glycoside receptors; D010042:Ouabain; D019061:src-Family Kinases; D048049:Extracellular Signal-Regulated MAP Kinases; D000254:Sodium-Potassium-Exchanging ATPase