title: The secretory KCa1.1 channel localises to crypts of distal mouse colon: functional and molecular evidence.
abstract: The colonic epithelium absorbs and secretes electrolytes and water. Ion and water absorption occurs primarily in surface cells, whereas crypt cells perform secretion. Ion transport in distal colon is regulated by aldosterone, which stimulates both Na(+) absorption and K(+) secretion. The electrogenic Na(+) absorption is mediated by epithelial Na(+) channel (ENaC) in surface cells. Previously, we identified the large conductance Ca(2+)-activated K(+) channel, K(Ca)1.1 or big potassium (BK) channel, as the only relevant K(+) secretory pathway in mouse distal colon. The exact localisation of K(Ca)1.1 channels along the crypt axis is, however, still controversial. The aim of this project was to further define the localisation of the K(Ca)1.1 channel in mouse distal colonic epithelium. Through quantification of mRNA extracted from micro-dissected surface and crypt cells, we confirmed that Na(+)/K(+)/2Cl(-) (NKCC1) is expressed primarily in the crypts and γ-ENaC primarily in the surface cells. The K(Ca)1.1 α-subunit mRNA was like NKCC1, mainly expressed in the crypts. The crypt to surface expression pattern of the channels and transporters was not altered when plasma aldosterone was elevated. The mRNA levels for NKCC1, γ-ENaC and K(Ca)1.1 α-subunit were, however, under these circumstances substantially augmented (K(Ca)1.1 α-subunit, twofold; NKCC1, twofold and ENaC, tenfold). Functionally, we show that ENaC-mediated Na(+) absorption and BK channel-mediated K(+) secretion are two independent processes. These findings show that K(Ca)1.1-mediated K(+) secretion mainly occurs in the crypts of the murine distal colon. This is in agreement with the general model of ion secretion being preferentially located to the crypt and not surface enterocytes.
authors.affiliation: Institute of Biomedicine, Physiology and Biophysics, The Water and Salt Research Center, Aarhus University, Ole Worms Allé 160, 8000, Aarhus C, Denmark.
authors.forename: Mads V
authors.initials: MV
authors.lastname: Sørensen
authors.forename: Anne B
authors.initials: AB
authors.lastname: Strandsby
authors.forename: Casper K
authors.initials: CK
authors.lastname: Larsen
authors.forename: Helle A
authors.initials: HA
authors.lastname: Praetorius
authors.forename: Jens
authors.initials: J
authors.lastname: Leipziger
mesh_terms: D000450:Aldosterone / Q000097:blood; D000818:Animals; D003106:Colon / Q000378:metabolism*; D053503:Epithelial Sodium Channels / Q000096:biosynthesis; D007413:Intestinal Mucosa / Q000378:metabolism*; D051037:Large-Conductance Calcium-Activated Potassium Channel alpha Subunits / Q000378:metabolism*; D051379:Mice; D012333:RNA, Messenger / Q000378:metabolism; D028021:Sodium-Potassium-Chloride Symporters / Q000096:biosynthesis; D064506:Solute Carrier Family 12, Member 2
chemical_list: D053503:Epithelial Sodium Channels; C465449:Kcnma1 protein, mouse; D051037:Large-Conductance Calcium-Activated Potassium Channel alpha Subunits; D012333:RNA, Messenger; C507053:Scnn1g protein, mouse; C578878:Slc12a2 protein, mouse; D028021:Sodium-Potassium-Chloride Symporters; D064506:Solute Carrier Family 12, Member 2; D000450:Aldosterone