Dynamic control of cystic fibrosis transmembrane conductance regulator Cl-/HCO3 - selectivity by external Cl -

Nikolay Shcheynikov, Kil Hwan Kim, Kyung Mi Kim, Michael R. Dorwart, Shigeru B H Ko, Hidemi Goto, Satoru Naruse, Philip J. Thomas, Shmuel Muallem

Research output: Contribution to journalArticle

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Abstract

HCO3 - secretion is a vital activity in cystic fibrosis transmembrane conductance regulator (CFTR)-expressing epithelia. However, the role of CFTR in this activity is not well understood. Simultaneous measurements of membrane potential and pHi and/or current in CFTR-expressing Xenopus oocytes revealed dynamic control of CFTR Cl -/HCO3 - permeability ratio, which is regulated by external Cl- (Clo -). Thus, reducing external Cl- from 110 to 0-10 mM resulted in the expected increase in membrane potential, but with no corresponding OH- or HCO 3 - influx. Approximately 3-4 min after reducing Cl o - to 0 mM, an abrupt switch in membrane potential occurs that coincided with an increased rates of OH- and HCO 3 - influx. The switch in membrane permeability to OH -/HCO3 - can also be recorded as a leftward shift in the reversal potential. Furthermore, an increased rate of OH - influx in response to elevating pHo to 9.0 was observed only after the switch in membrane potential. The time to switch increased to 11 min at Clo - of 5 mM. Conversely, re-addition of external Cl- after the switch in membrane potential did not stop HCO 3 - influx, which continued for about 3.9 min after Cl - addition. Importantly, addition of external Cl- to cells incubated in Cl--free medium never resulted in HCO 3 - efflux. Voltage and current clamp experiments showed that the delayed HCO3 - transport is electrogenic. These results indicate that CFTR exists in two conformations, a Cl- only and a Cl- and OH-/HCO3 - permeable state. The switch between the states is controlled by external Cl-. Accordingly, a different tryptic pattern of CFTR was found upon digestion in Cl--containing and Cl--free media. The physiological significance of these finding is discussed in the context of HCO 3 - secretion by tissues such as the pancreas and salivary glands.

Original languageEnglish (US)
Pages (from-to)21857-21865
Number of pages9
JournalJournal of Biological Chemistry
Volume279
Issue number21
DOIs
StatePublished - May 21 2004

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Cystic Fibrosis Transmembrane Conductance Regulator
Membrane Potentials
Switches
Membranes
Permeability
Clamping devices
Xenopus
Salivary Glands
Oocytes
Conformations
Pancreas
Digestion
Epithelium
hydroxide ion
Tissue
Electric potential

ASJC Scopus subject areas

  • Biochemistry

Cite this

Shcheynikov, N., Kim, K. H., Kim, K. M., Dorwart, M. R., Ko, S. B. H., Goto, H., ... Muallem, S. (2004). Dynamic control of cystic fibrosis transmembrane conductance regulator Cl-/HCO3 - selectivity by external Cl - Journal of Biological Chemistry, 279(21), 21857-21865. https://doi.org/10.1074/jbc.M313323200

Dynamic control of cystic fibrosis transmembrane conductance regulator Cl-/HCO3 - selectivity by external Cl - . / Shcheynikov, Nikolay; Kim, Kil Hwan; Kim, Kyung Mi; Dorwart, Michael R.; Ko, Shigeru B H; Goto, Hidemi; Naruse, Satoru; Thomas, Philip J.; Muallem, Shmuel.

In: Journal of Biological Chemistry, Vol. 279, No. 21, 21.05.2004, p. 21857-21865.

Research output: Contribution to journalArticle

Shcheynikov, N, Kim, KH, Kim, KM, Dorwart, MR, Ko, SBH, Goto, H, Naruse, S, Thomas, PJ & Muallem, S 2004, 'Dynamic control of cystic fibrosis transmembrane conductance regulator Cl-/HCO3 - selectivity by external Cl - ', Journal of Biological Chemistry, vol. 279, no. 21, pp. 21857-21865. https://doi.org/10.1074/jbc.M313323200
Shcheynikov, Nikolay ; Kim, Kil Hwan ; Kim, Kyung Mi ; Dorwart, Michael R. ; Ko, Shigeru B H ; Goto, Hidemi ; Naruse, Satoru ; Thomas, Philip J. ; Muallem, Shmuel. / Dynamic control of cystic fibrosis transmembrane conductance regulator Cl-/HCO3 - selectivity by external Cl - In: Journal of Biological Chemistry. 2004 ; Vol. 279, No. 21. pp. 21857-21865.
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