title: Epithelial Sodium Channel-Mediated Sodium Transport Is Not Dependent on the Membrane-Bound Serine Protease CAP2/Tmprss4.
abstract: The membrane-bound serine protease CAP2/Tmprss4 has been previously identified in vitro as a positive regulator of the epithelial sodium channel (ENaC). To study its in vivo implication in ENaC-mediated sodium absorption, we generated a knockout mouse model for CAP2/Tmprss4. Mice deficient in CAP2/Tmprss4 were viable, fertile, and did not show any obvious histological abnormalities. Unexpectedly, when challenged with sodium-deficient diet, these mice did not develop any impairment in renal sodium handling as evidenced by normal plasma and urinary sodium and potassium electrolytes, as well as normal aldosterone levels. Despite minor alterations in ENaC mRNA expression, we found no evidence for altered proteolytic cleavage of ENaC subunits. In consequence, ENaC activity, as monitored by the amiloride-sensitive rectal potential difference (ΔPD), was not altered even under dietary sodium restriction. In summary, ENaC-mediated sodium balance is not affected by lack of CAP2/Tmprss4 expression and thus, does not seem to directly control ENaC expression and activity in vivo.
authors: Department of Pharmacology & Toxicology, University of Lausanne, Lausanne, Switzerland.
authors: Anna
authors: A
authors: Keppner
authors: Department of Pharmacology & Toxicology, University of Lausanne, Lausanne, Switzerland.
authors: Ditte
authors: D
authors: Andreasen
authors: Department of Pharmacology & Toxicology, University of Lausanne, Lausanne, Switzerland.
authors: Anne-Marie
authors: AM
authors: Mérillat
authors: Department of Pharmacology & Toxicology, University of Lausanne, Lausanne, Switzerland.
authors: Julie
authors: J
authors: Bapst
authors: Department of Pharmacology & Toxicology, University of Lausanne, Lausanne, Switzerland.
authors: Camille
authors: C
authors: Ansermet
authors: Department of Medicine/Division of Nephrology and Hypertension, Lausanne University Hospital (CHUV), Lausanne, Switzerland; Department of Medicine/Physiology, University of Fribourg, Fribourg, Switzerland.
authors: Qing
authors: Q
authors: Wang
authors: Department of Medicine/Division of Nephrology and Hypertension, Lausanne University Hospital (CHUV), Lausanne, Switzerland.
authors: Marc
authors: M
authors: Maillard
authors: Department of Pharmacology & Toxicology, University of Lausanne, Lausanne, Switzerland.
authors: Sumedha
authors: S
authors: Malsure
authors: Institut Universitaire de Pathologie, Lausanne University Hospital (CHUV), Lausanne, Switzerland.
authors: Antoine
authors: A
authors: Nobile
authors: Department of Pharmacology & Toxicology, University of Lausanne, Lausanne, Switzerland.
authors: Edith
authors: E
authors: Hummler
mesh_terms: D065966:Absorption, Physicochemical; D000818:Animals; D001692:Biological Transport; D002462:Cell Membrane / Q000378:metabolism*; D053503:Epithelial Sodium Channels / Q000378:metabolism*; D055786:Gene Knockout Techniques; D006706:Homeostasis; D008565:Membrane Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D012697:Serine Endopeptidases / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D012964:Sodium / Q000378:metabolism*
chemical_list: D053503:Epithelial Sodium Channels; D008565:Membrane Proteins; D012964:Sodium; D012697:Serine Endopeptidases; C470745:Tmprss4 protein, mouse