title: Role of BKbeta1 in Na+ reabsorption by cortical collecting ducts of Na+-deprived mice.
abstract: On a low-Na(+) diet (LNa(+)), urinary Na(+) loss is prevented by aldosterone-induced Na(+) reabsorption through epithelial Na(+) channels (ENaC) in the connecting tubules (CNT) and cortical collecting ducts (CCD). However, the mechanism whereby K(+) loss is minimized and Na(+) reabsorption is maximized in the face of a reduced lumen-to-bath Na(+) gradient is not fully understood. The large-conductance calcium-activated potassium channel (BK)beta1 subunit (gene: Kcnmb1), which has a role in K(+) secretion in the CNT, is absent in the CCD in mice on a control diet. We hypothesized that BKalpha/beta1 helps to maximize Na(+) reabsorption during Na(+) deficiency. With LNa(+), the Na(+) clearance of Kcnmb1-mutant mice (Kcnmb1(-/-)) was 45% greater and the plasma Na(+) concentration and osmolality were significantly reduced compared with wild-type mouse (WT) controls. On LNa(+), Kcnmb1(-/-) exhibited exacerbated volume depletion (higher Hct and weight loss) compared with WT. LNa(+), which did not affect the mean arterial blood pressure (MAP) of WT, significantly reduced MAP of Kcnmb1(-/-). The plasma aldosterone concentration of Kcnmb1(-/-) on LNa(+) was significantly elevated compared with Kcnmb1(-/-) on a control diet but was not different from WT on LNa(+). Immunohistochemical staining revealed that BKalpha and BKbeta1, which were absent in the principal cells (PCs) of the CCD, were localized on the basolateral membrane (BSM) of PCs of WT on LNa(+). Moreover, BKalpha was absent from the BSM of PCs of Na(+)-deficient Kcnmb1(-/-). We conclude that part of the mechanism to maximize Na(+) reabsorption during Na(+) deficiency is the placement of BKalpha/beta1 channels in the BSM of CCD PCs.
authors.affiliation: Department of Cellular and Integrative Physiology, University of Nebraska Medical Center, Omaha, Nebraska 68198-5850, USA.
authors.forename: P Richard
authors.initials: PR
authors.lastname: Grimm
authors.forename: Debra L
authors.initials: DL
authors.lastname: Irsik
authors.forename: Liping
authors.initials: L
authors.lastname: Liu
authors.forename: J David
authors.initials: JD
authors.lastname: Holtzclaw
authors.forename: Steven C
authors.initials: SC
authors.lastname: Sansom
mesh_terms: D000450:Aldosterone / Q000097:blood; D000818:Animals; D001692:Biological Transport; D001794:Blood Pressure; D002462:Cell Membrane / Q000378:metabolism; D003404:Creatinine / Q000097:blood; D004039:Diet, Sodium-Restricted; D007010:Hyponatremia / Q000097:blood*; D007685:Kidney Tubules, Collecting / Q000378:metabolism*; D051038:Large-Conductance Calcium-Activated Potassium Channel beta Subunits / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009994:Osmolar Concentration; D010953:Plasma Volume; D011188:Potassium / Q000097:blood / Q000378:metabolism* / Q000652:urine; D021381:Protein Transport; D012964:Sodium / Q000097:blood / Q000378:metabolism* / Q000652:urine; D012982:Sodium, Dietary / Q000378:metabolism; D014563:Urodynamics; D014882:Water-Electrolyte Balance
chemical_list: C543091:Kcnmb1 protein, mouse; C494843:Kcnmb4 protein, mouse; D051038:Large-Conductance Calcium-Activated Potassium Channel beta Subunits; D012982:Sodium, Dietary; D000450:Aldosterone; D012964:Sodium; D003404:Creatinine; D011188:Potassium