Voltage-sensitive gating induced by a mutation in the fifth transmembrane domain of CFTR

Zhi Ren Zhang, Shawn Zeltwanger, Stephen S. Smith, David C. Dawson, Nael A. Mccarty

Research output: Contribution to journalArticle

9 Scopus citations

Abstract

A mutation in the fifth transmembrane domain of the cystic fibrosis transmembrane conductance regulator (CFTR) Cl- channel (V317E) resulted in whole cell currents that exhibited marked outward rectification on expression in Xenopus oocytes. However, the single-channel unitary current (i)-voltage (V) relationship failed to account for the rectification of whole cell currents. In excised patches containing one to a few channels, the time-averaged single-channel current (I)-V relationship (I = N × Po × i, where N is the number of active channels and Po is open probability) of V317E CFTR displayed outward rectification, whereas that of wild-type CFTR was linear, indicating that the Po of V317E CFTR is voltage dependent. The decrease in Po at negative potentials was due to both a decreased burst duration and a decreased opening rate that could not be ameliorated by a 10-fold increase in ATP concentration. This behavior appears to reflect a true voltage dependence of the gating process because the Po-V relationship did not depend on the direction of Cl- movement. The results are consistent with the introduction, by a point mutation, of a novel voltage-dependent gating mode that may provide a useful tool for probing the portions of the protein that move in response to ATP-dependent gating.

Original languageEnglish (US)
Pages (from-to)L135-L145
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume282
Issue number1 26-1
StatePublished - Jun 29 2002

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Keywords

  • Chloride channel
  • Cystic fibrosis transmembrane conductance regulator
  • Voltage dependence

ASJC Scopus subject areas

  • Physiology
  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology

Cite this

Zhang, Z. R., Zeltwanger, S., Smith, S. S., Dawson, D. C., & Mccarty, N. A. (2002). Voltage-sensitive gating induced by a mutation in the fifth transmembrane domain of CFTR. American Journal of Physiology - Lung Cellular and Molecular Physiology, 282(1 26-1), L135-L145.