Deactivation of cftr -cl conductance by endogenous phosphatases in
the native sweat duct.
Reddy, M. M., and P. M. Quinton.
Division of Biomedical Sciences, University of California,
Riverside, Riverside, CA- 92521
APStracts 2:0288C, 1995.
CFTR (cystic fibrosis transmembrane conductance regulator) is a
phosphorylation activated Cl channel. However, very little is known
about the endogenous mechanism(s) of deactivation of CFTR -GCl (CFTR-
Cl conductance) in vivo. We studied the action of endogenous
phosphatases in regulating the cAMP and ATP induced CFTR-GCl in the
apical membrane of microperfused preparations of basolaterally
permeabilized native sweat duct. Activation of CFTR-GCl was monitored
by measuring the apical Cl diffusion potentials (VCl) and Cl
conductance (GCl) which spontaneously deactivated upon removal of
cAMP. This spontaneous loss of CFTR-GCl activity could be prevented
by a cocktail of phosphatase inhibitors (fluoride, vanadate and
okadaic acid). We studied the effects of each of these phosphatase
antagonists on the rate of deactivation of CFTR-GCl following cAMP
wash out. In contrast to vanadate or fluoride, okadaic acid virtually
prevented deactivation of CFTR-GCl following cAMP wash out. We
conclude that either or both protein phosphatase PP 1 and PP 2A are
responsible for the dephosphorylation deactivation of CFTR-GCl in
vivo.
Received 3 January 1995; accepted in final form 18 July 1995.
APS Manuscript Number C4-5.
Article publication pending Am. J. Physiol. (Cell Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 10 August 1995.