Preventing Thermal Inactivation of ΔF508-CFTR Channel Activity by NBD1 Suppressor Mutations and by Constitutively Active Intracellular Loop Mutations

Abstract

ΔF508 is a temperature sensitive CFTR mutant that causes cystic fibrosis by disrupting CFTR processing, trafficking and channel gating. To address the question of thermal stability of ΔF508-CFTR channel gating, we examined WT- and ΔF508-CFTR channel activity in excised patches at varying temperature (23 to 36°C) with or without exposure to CFTR correctors and potentiators. In addition, constructs that combined the ΔF508 mutation with intracellular loop mutations that promote ATP-independent channel gating and with NBD1 suppressor mutations that enhance ΔF508-CFTR biosynthetic maturation were examined under the same conditions.