The vast majority of cases of cystic Þbrosis are the result of a single amino acid deletion (DF508) in the sequence of CFTR. The result of this deletion is that the DF-CFTR misfolds and does not obtain its normal residence in the plasma membrane of cells, but instead is proteolyzed. The F508-contain
Poster Session Abstracts: Abstracts 149–215
- Publisher
- John Wiley and Sons
- Year
- 1998
- Tongue
- English
- Weight
- 335 KB
- Volume
- 26
- Category
- Article
- ISSN
- 8755-6863
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✦ Synopsis
The nasal potential difference (PD) technique allows measurement of airway ion transport in human subjects in vivo. The characteristic abnormalities found in CF, namely increased Na + absorption and decreased cAMP-regulated Cl -secretion can be measured by sequential perfusion with amiloride, low Cl -and isoproterenol solutions (Eur Respir J 1994;7:2050). In non-CF airways, the response to a low Cl - solution is a sustained hyperpolarisation lasting at least 5 minutes. In contrast, CF subjects often demonstrate an initial transient hyperpolarisation, attributed to Ca 2+ -regulated Cl -channels, but no sustained response. To further evaluate the CF responses, we have altered the concentrations of Ca 2+ & Mg 2+ in the perfusate and measured the Cl - secretory response using the nasal PD. CF subjects were studied on separate days with (i) standard Krebs diluent (Ca 2+ 2 mM, Mg 2+ 1 mM), (ii) nominally divalent-free diluent, or (iii) diluent containing Mg 2+ (but not Ca 2+ ). In the presence of divalent ions, there was no sustained hyperpolarisation following low Cl -perfusion [mean (SEM): -0.4 (0.7) mV]. However, in the absence of divalent ions the Cl - response demonstrated a signiÞcant hyperpolarisation [8.0 (0.7) mV, p<0.01, n=7]. In the 1mM Mg 2+ , Ca 2+ -free diluent there was a hyperpolarisation of 8.6 (2.4) mV, n=6. However, there was no increase in isoproterenol responses with either divalent free or Ca 2+ -free diluents. This suggests that extracellular Ca 2+ but not Mg 2+ may be involved in the Cl -impermeability found in the CF airway epithelium.
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