The theoretical basis for the efficacy of amiloride treatment of cystic fibrosis

E. Jakobsson, J. A. Novotny

Research output: Contribution to journalArticlepeer-review

Abstract

We have constructed a computational model for ion-water flu) coupling in the airway epithelium (Novotny and Jakobsson, Am. J. Physiol, in press). Our computer model demonstrates the role played by each particular ion transport mechanism in contributing to water movement. The basolateral sodium-potassium pump, K channels, and NaK2Cl cotransporter all play significant roles in facilitating water secretion, in addition to the apical chloride channels. By contrast, apical sodium channels are found to reduce water secretion. In agreement with experiment and clinical experience, water transport in the model is inhibited by reduced apical chloride permeability, mimicking the effects of the cystic fibrosis genetic defect. In the model it is found that blocking the apical amiloride-sensitive sodium permeability can completely compensate for the reduced apical chloride permeability characteristic of cystic fibrosis, restoring normal water movement. Thus the simulations suggest that if amiloride can be delivered to the apical membrane in appropriate dosage, the airway symptoms of cystic fibrosis might be substantially, possibly even completely, alleviated. Early clinical trials of amiloride, which had promising results, predated the identification of the cystic fibrosis genetic defect in the apical chloride channel. The simulation results suggest that .even though the genetic defect is in the chloride channel, the sodium channel might be a suitable target for effective therapy.

Original languageEnglish (US)
Pages (from-to)A92
JournalFASEB Journal
Volume10
Issue number3
StatePublished - Dec 1 1996

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

Fingerprint Dive into the research topics of 'The theoretical basis for the efficacy of amiloride treatment of cystic fibrosis'. Together they form a unique fingerprint.

Cite this