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The amiloride-inhibitable Na+ conductance is reduced by the cystic fibrosis transmembrane conductance regulator in normal but not in cystic fibrosis airways.
J Clin Invest. 1998 Jul 01; 102(1):15-21.JCI

Abstract

Cystic fibrosis (CF) airway cells, besides their well-known defect in cAMP-dependent Cl- conductance, are characterized by an enhanced Na+ conductance. In this study we have examined the Na+ conductance in human respiratory tract by measuring transepithelial voltage and resistance (Vte, Rte) and by assessing membrane voltages (Vm) of freshly isolated airway epithelial cells from CF and non-CF patients. Basal amiloride inhibitable (10 micromol/liter) equivalent short circuit current (Isc = Vte/Rte) was significantly increased in CF compared with non-CF tissues. After stimulation by forskolin (10 micromol/liter) a significant depolarization of Vm corresponding to the cAMP-dependent activation of a Cl- conductance was observed in non-CF but not in CF airway cells. In non-CF tissue but not in CF tissue the effects of amiloride and N-methyl-D-glucamine on Vm were attenuated in the presence of forskolin. Also the amiloride-inhibitable Isc was significantly reduced by forskolin (1 micromol/liter) and isobutylmethylxanthine (IBMX; 100 micromol/liter) only in non-CF tissue. We conclude that cystic fibrosis transmembrane conductance regulator acts as a downregulator of epithelial Na+ channels in human airways. This downregulation of epithelial Na+ channels is absent in CF airways, leading to hyperabsorption and to the characteristic increase in mucus viscosity.

Authors+Show Affiliations

Physiologisches Institut, Albert-Ludwigs-Universität Freiburg, 79104 Freiburg, Germany.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

9649552

Citation

Mall, M, et al. "The Amiloride-inhibitable Na+ Conductance Is Reduced By the Cystic Fibrosis Transmembrane Conductance Regulator in Normal but Not in Cystic Fibrosis Airways." The Journal of Clinical Investigation, vol. 102, no. 1, 1998, pp. 15-21.
Mall M, Bleich M, Greger R, et al. The amiloride-inhibitable Na+ conductance is reduced by the cystic fibrosis transmembrane conductance regulator in normal but not in cystic fibrosis airways. J Clin Invest. 1998;102(1):15-21.
Mall, M., Bleich, M., Greger, R., Schreiber, R., & Kunzelmann, K. (1998). The amiloride-inhibitable Na+ conductance is reduced by the cystic fibrosis transmembrane conductance regulator in normal but not in cystic fibrosis airways. The Journal of Clinical Investigation, 102(1), 15-21.
Mall M, et al. The Amiloride-inhibitable Na+ Conductance Is Reduced By the Cystic Fibrosis Transmembrane Conductance Regulator in Normal but Not in Cystic Fibrosis Airways. J Clin Invest. 1998 Jul 1;102(1):15-21. PubMed PMID: 9649552.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The amiloride-inhibitable Na+ conductance is reduced by the cystic fibrosis transmembrane conductance regulator in normal but not in cystic fibrosis airways. AU - Mall,M, AU - Bleich,M, AU - Greger,R, AU - Schreiber,R, AU - Kunzelmann,K, PY - 1998/7/3/pubmed PY - 1998/7/3/medline PY - 1998/7/3/entrez SP - 15 EP - 21 JF - The Journal of clinical investigation JO - J. Clin. Invest. VL - 102 IS - 1 N2 - Cystic fibrosis (CF) airway cells, besides their well-known defect in cAMP-dependent Cl- conductance, are characterized by an enhanced Na+ conductance. In this study we have examined the Na+ conductance in human respiratory tract by measuring transepithelial voltage and resistance (Vte, Rte) and by assessing membrane voltages (Vm) of freshly isolated airway epithelial cells from CF and non-CF patients. Basal amiloride inhibitable (10 micromol/liter) equivalent short circuit current (Isc = Vte/Rte) was significantly increased in CF compared with non-CF tissues. After stimulation by forskolin (10 micromol/liter) a significant depolarization of Vm corresponding to the cAMP-dependent activation of a Cl- conductance was observed in non-CF but not in CF airway cells. In non-CF tissue but not in CF tissue the effects of amiloride and N-methyl-D-glucamine on Vm were attenuated in the presence of forskolin. Also the amiloride-inhibitable Isc was significantly reduced by forskolin (1 micromol/liter) and isobutylmethylxanthine (IBMX; 100 micromol/liter) only in non-CF tissue. We conclude that cystic fibrosis transmembrane conductance regulator acts as a downregulator of epithelial Na+ channels in human airways. This downregulation of epithelial Na+ channels is absent in CF airways, leading to hyperabsorption and to the characteristic increase in mucus viscosity. SN - 0021-9738 UR - https://www.unboundmedicine.com/medline/citation/9649552/The_amiloride_inhibitable_Na+_conductance_is_reduced_by_the_cystic_fibrosis_transmembrane_conductance_regulator_in_normal_but_not_in_cystic_fibrosis_airways_ L2 - https://doi.org/10.1172/JCI2729 DB - PRIME DP - Unbound Medicine ER -