Rectification of whole-cell cftr chloride current.
Overholt, Jeffrey L., Ann Saulino, Mitchell L. Drumm, and Robert D. Harvey.
Departments of Physiology and Biophysics, Pediatrics, and Genetics, Case
Western Reserve University, Cleveland, Ohio 44106, Telephone: (216) 368-8938,
Fax: (216) 368-5586, E-Mail: jxo2@po.cwru.edu
APStracts 2:0020C, 1995.
Whole-cell epithelial CFTR Cl- currents exhibited a linear current-voltage (I
-V) relationship with high symmetrical transmembrane Cl- concentrations.
However, when intracellular Cl- (Cl-i) was reduced by replacement with
glutamate, I-V relationships were outwardly rectifying. Rectification was not
affected by reducing extracellular Cl- to eliminate or reverse the gradient,
indicating that rectification is not a function of the Cl- gradient.
Rectification was affected by Cl-i in a concentration dependent manner, and
it was weaker when Cl-i was reduced by replacement with sucrose. These
characteristics are identical to those of the cardiac isoform of CFTR, and
the experimental data could be simulated by an Eyring rate theory model
assuming that permeating anions interact at a single binding site within the
channel pore. No evidence was found for multiple binding sites. These results
indicate that rectification is a function of the concentration and
permeability of the anions inside the cell. It is concluded that
rectification of CFTR Cl- current is a property of ion channel permeation
that would occur under physiological conditions, and permeation of the
epithelial and cardiac isoforms of CFTR is identical.
Received 15 July 1994; accepted in final form 23 September 1994
APS Manuscript Number C403-4.
Article publication pending Am. J. Physiol. (Cell Physiology).
ISSN 1080-4757 Copyright 1994 The American Physiological Society.
Published in APStracts on 27 February 1995.