title: Maxi K+ channels co-localised with CFTR in the apical membrane of an exocrine gland acinus: possible involvement in secretion.
abstract: The primary secretion formed in various exocrine glands has a [K+] 2-5 times that of plasma. In this study we measured the transepithelial flux of 36Cl-, 22Na+ and 42K+ across the frog skin and applied the single-channel patch-clamp technique to the apical membrane of frog skin gland acini to investigate the pathway taken by K+ secreted by the glands. Transepithelial K+ secretion was active and was driven by a larger force than the secretion of Na+. When driving Na+ through the epithelium by clamping the transepithelial potential to 100 mV (apical solution reference), blockers of cellular secretion (apical 5-nitro-2-(3-phenylpropylamino)benzoate or basolateral quinine or furosemide) decreased K+ secretion but left Na+ secretion unaffected. We conclude that K+ follows a transcellular pathway across the epithelium. Patch-clamp analysis of the apical membrane of microdissected gland acini revealed a population of voltage- and calcium-activated K+ channels of the maxi K+ type. In cell-attached patches these channels were activated by membrane potential depolarisation or exposure to prostaglandin E2 and had a permeability of 3.6 +/- 0.3 x 10(-13) cm3 s-1, giving a calculated conductance of 170 pS with 125 mM K+ on both sides of the membrane. In inside-out patches the channels were activated by increasing intracellular [Ca2+] from 10(-7) to 10(-6) M and were blocked by Ba2+ added to the cytoplasmic side. Exposure of inside-out patches containing the maxi K+ channel to ATP on the inside activated cystic fibrosis transmembrane conductance regulator (CFTR) Cl- channels, confirming that both channels are co-localised to the apical membrane. We interpret these findings in terms of a model where transepithelial NaCl secretion can be supported in part by an apical K+ conductance.
authors.affiliation: August Krogh Institute, Universitetsparken 13, 2100 Copenhagen Ø, Denmark.
authors.forename: J B
authors.initials: JB
authors.lastname: Sørensen
authors.forename: M S
authors.initials: MS
authors.lastname: Nielsen
authors.forename: C N
authors.initials: CN
authors.lastname: Gudme
authors.forename: E H
authors.initials: EH
authors.lastname: Larsen
authors.forename: R
authors.initials: R
authors.lastname: Nielsen
mesh_terms: D000584:Amiloride / Q000494:pharmacology; D000818:Animals; D001464:Barium / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology; D002462:Cell Membrane / Q000737:chemistry* / Q000502:physiology; D018118:Chloride Channels / Q000037:antagonists & inhibitors / Q000502:physiology; D002712:Chlorides / Q000378:metabolism; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000032:analysis* / Q000187:drug effects; D015232:Dinoprostone / Q000494:pharmacology; D004553:Electric Conductivity; D004848:Epithelium / Q000378:metabolism; D005088:Exocrine Glands / Q000737:chemistry*; D005260:Female; D005665:Furosemide / Q000494:pharmacology; D008297:Male; D008564:Membrane Potentials; D009579:Nitrobenzoates / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D011188:Potassium / Q000378:metabolism; D015221:Potassium Channels / Q000032:analysis* / Q000187:drug effects; D011893:Rana esculenta; D012867:Skin / Q000737:chemistry* / Q000378:metabolism; D012964:Sodium / Q000378:metabolism
chemical_list: D018118:Chloride Channels; D002712:Chlorides; D009579:Nitrobenzoates; D015221:Potassium Channels; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D001464:Barium; C058176:5-nitro-2-(3-phenylpropylamino)benzoic acid; D000584:Amiloride; D005665:Furosemide; D012964:Sodium; D015232:Dinoprostone; D011188:Potassium; D002118:Calcium