Maxi K+ channels co-localised with CFTR in the apical membrane of an exocrine gland acinus: possible involvement in secretion

Citation
Jb. Sorensen et al., Maxi K+ channels co-localised with CFTR in the apical membrane of an exocrine gland acinus: possible involvement in secretion, PFLUG ARCH, 442(1), 2001, pp. 1-11
Citations number
27
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Physiology
Journal title
PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY
ISSN journal
0031-6768 → ACNP
Volume
442
Issue
1
Year of publication
2001
Pages
1 - 11
Database
ISI
SICI code
0031-6768(200104)442:1<1:MKCCWC>2.0.ZU;2-U
Abstract
The primary secretion formed in various exocrine glands has a [K+] 2-5 time s that of plasma. In this study we measured the transepithelial flux of Cl- 36(-), Na-22(+) and K-42(+) across the frog skin and applied the single-cha nnel patch-clamp technique to the apical membrane of frog skin gland acini to investigate the pathway taken by K+ secreted by the glands. Transepithel ial K+ secretion was active and was driven by a larger force than the secre tion of Na+. When driving Na+ through the epithelium by clamping the transe pithelial potential to 100 mV (apical solution reflectance), blockers of ce llular secretion (apical 5-nitro-2-(3-phenylpropylamino)benzoate or basolat eral quinine or furosemide) decreased K+ secretion but left Na+ secretion u naffected. We conclude that K+ follows a transcellular pathway across the e pithelium. Patch-clamp analysis of the apical membrane of microdissected gl and acini revealed a population of voltage- and calcium-activated K+ channe ls of the maxi K+ type. In cell-attached patches these channels were activa ted by membrane potential depolarisation or exposure to prostaglandin E-2 a nd had a permeability of 3.6 +/-0.3x10(-13) cm(3) s(-1), giving a calculate d conductance of 170 pS with 125 mM K+ on both sides of the membrane. In in side-out patches the channels were activated by increasing intracellular [C a2+] from 10(-7) to 10(-6) M and were blocked by Ba2+ added to the cytoplas mic side. Exposure of inside-out patches containing the maxi K+ channel to ATP on the inside activated cystic fibrosis transmembrane conductance regul ator (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+ co nductance.