ABCMdb

PMID: 19865788

Reddy MM, Quinton PM
PKA mediates constitutive activation of CFTR in human sweat duct.
J Membr Biol. 2009 Oct;231(2-3):65-78. Epub 2009 Oct 29., [PubMed]

Sentences

No. Mutations Sentence Comment

9 ABCC7 p.Arg117His Keywords CFTR Á DF508 CFTR Á R117H CFTR Á PKA Á PKG Á G proteins Á Glutamate Á a-toxin Á Okadaic acid Introduction Generally, epithelial ion channels are thought to be activated by neurohumoral stimuli in response to electrolyte transport demand but to remain inactive in the absence of such stimuli. Login to comment 91 ABCC7 p.Arg117His Sweat Ducts from DF508/DF508 CF Subjects Sweat ducts from homozygous (DF508/DF508) or heterozygous (DF508/R117H) CF subjects were initially perfused with 150 mM NaCl in the bath and 150 mM NaCl ? Login to comment 97 ABCC7 p.Arg117His ABCC7 p.Arg117His Sweat Ducts from R117H/DF508 CF Subjects We noticed significant depolarization of transepithelial potential of heterozygous (DF508/R117H) CF ducts when bath NaCl was replaced with KGlu (Fig. 3b), although the magnitude of depolarization of these compound heterozygous CF ducts was relatively smaller compared to that of normal ducts (Figs. 1a, 3b). Login to comment 98 ABCC7 p.Arg117His In contrast to the lack of electrical response of DF508 homozygous CF ducts, the application of a-toxin induced qualitatively similar electrical responses in heterozygous (DF508/R117H, i.e., gradual increase in transepithelial resistance corresponding with pore formation and loss of intracellular messengers) as observed in normal ducts (Figs. 1a, 3b). Login to comment 119 ABCC7 p.Arg117His b In contrast to the homozygous CF ducts, heterozygous CF ducts with R117H/DF508 mutations showed a small but consistent depolarization to the imposed Cl-gradient. Login to comment 121 ABCC7 p.Arg117His These results are consistent with the fact that R117H CF mutation retains residual Cl-conductance. Login to comment 220 ABCC7 p.Arg117His (C) and (L) represent cytosolic bath and lumen, respectively (Fig. 3a) or significantly smaller (in heterozygous R117H/ DF508 CF ducts that partially express CFTR activity) (Reddy and Quinton 2003) (Fig. 3b) compared to non-CF ducts (Fig. 1). Login to comment 221 ABCC7 p.Arg117His Furthermore, permeabilization of the basolateral membrane with a-toxin either had no effect in homozygous DF508 CF ducts (Fig. 3a) or had qualitatively similar but quantitatively smaller effects on transepithelial potential or conductance of R117H/DF508 CF ducts, which is consistent with reduced gCFTR in these ducts. Login to comment