Na/K-ATPase endocytosis couples pumping and leaking activities in renal epithelial cells: a hypothesis.
Renal adaptation to acute or chronic volume expansion as well as dietary sodium intake involves a marked decrease in proximal tubule sodium transport. The precise molecular mechanisms involved in this alteration in proximal tubule sodium transport are still unclear. Low concentration of ouabain, a cardiotonic steroid (CTS) that is a specific inhibitor as well as a ligand of the Na/K-ATPase, has been shown to significantly inhibit transepithelial Na+ transport without altering the intracellular Na+ concentration ([Na+]i) in LLC-PK1 cells. This process is mediated by ouabain-activated signaling pathways that stimulate the endocytosis of the basolateral Na/K-ATPase and down-regulation of apical NHE3 (Na/H exchanger isoform 3). Thus, we propose that CTS, such as ouabain and marinobufagenin (MBG), are intimately involved in renal proximal tubule adaptations to volume expansion. We further speculate that CTS-induced Na/K-ATPase endocytosis couples pumping and leaking activities in renal epithelial cells.
Liu
Jiang
J
Department of Medicine, College of Medicine, University of Toledo, Toledo, Ohio 43614, USA. jiang.liu@utoledo.edu
D000818:Animals; D002316:Cardiotonic Agents / Q000378:metabolism* / Q000494:pharmacology; D002460:Cell Line; D016764:Cell Polarity / Q000502:physiology; D004705:Endocytosis / Q000502:physiology*; D004847:Epithelial Cells / Q000502:physiology*; D006801:Humans; D017136:Ion Transport; D007687:Kidney Tubules, Proximal / Q000502:physiology; D008954:Models, Biological; D010042:Ouabain / Q000378:metabolism* / Q000494:pharmacology; D015398:Signal Transduction; D012964:Sodium / Q000378:metabolism; D017923:Sodium-Hydrogen Exchangers / Q000502:physiology*; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors / Q000502:physiology*
D002316:Cardiotonic Agents; D017923:Sodium-Hydrogen Exchangers; D010042:Ouabain; D012964:Sodium; D000254:Sodium-Potassium-Exchanging ATPase