title: Renal fluid and electrolyte handling in BKCa-beta1-/- mice.
abstract: Large-conductance Ca(2+)-activated K(+) channels (BK(Ca)) are composed of pore-forming alpha-subunits and one of four accessory beta-subunits. The beta1-subunit, found predominantly in smooth muscle, modulates the Ca(2+) sensitivity and pharmacological properties of BK(Ca). BK(Ca)-beta1 null mice (Mbeta1(-/-)) are moderately hypertensive, consistent with the role of BK(Ca) in modulating intrinsic vascular tone. Because BK(Ca) are present in various renal cells including the mesangium and cortical collecting ducts, we determined whether fluid or electrolyte excretion was impaired in Mbeta1(-/-) under euvolemic, volume-expanded, or high-salt diet conditions. Under euvolemic conditions, no differences in renal function were found between Mbeta1(-/-) and Mbeta1(+/+). However, glomerular filtration rate (GFR) and fractional K(+) excretion were significantly impaired in Mbeta1(-/-) in response to acute volume expansion. In contrast, Mbeta1(-/-) exhibited enhanced Na(+) excretion and fractional Na(+) excretion responses to acute volume expansion. Differences in renal function between Mbeta1(+/+) and Mbeta1(-/-) were not observed when chronically treated with a high-salt diet. These observations indicate that the beta1-subunit of BK(Ca) contributes to the increased GFR that accompanies an acute salt and volume load and raises the possibility that it is also involved in regulating K(+) excretion under these conditions.
authors.affiliation: Department of Physiology and Biophysics, University of Nebraska Medical Center, Omaha, Nebraska 68198-4575, USA.
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Pluznick
authors.forename: Peilin
authors.initials: P
authors.lastname: Wei
authors.forename: Pamela K
authors.initials: PK
authors.lastname: Carmines
authors.forename: Steven C
authors.initials: SC
authors.lastname: Sansom
mesh_terms: D000818:Animals; D009320:Atrial Natriuretic Factor / Q000494:pharmacology; D001794:Blood Pressure / Q000502:physiology; D001826:Body Fluids / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D004573:Electrolytes / Q000378:metabolism; D005260:Female; D016650:Fluorescein-5-isothiocyanate; D005456:Fluorescent Dyes; D005919:Glomerular Filtration Rate; D007444:Inulin; D007668:Kidney / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010812:Physical Stimulation; D011188:Potassium / Q000378:metabolism; D024681:Potassium Channels, Calcium-Activated / Q000235:genetics / Q000502:physiology*; D012079:Renal Circulation / Q000235:genetics / Q000502:physiology; D012964:Sodium / Q000378:metabolism
chemical_list: D004573:Electrolytes; D005456:Fluorescent Dyes; D024681:Potassium Channels, Calcium-Activated; D009320:Atrial Natriuretic Factor; D007444:Inulin; D012964:Sodium; D016650:Fluorescein-5-isothiocyanate; D011188:Potassium; D002118:Calcium