A src-like kinase activates outwardly rectifying chloride channels in CFTR-defective lymphocytes

Defective activation of chloride channels is a hallmark of cystic fibrosis (CF). Recently we have described activation of a volume-sensitive, outwardl y rectifying chloride conductance (I-OR) through the src-like tyrosine kina se p56(lck). Here we show that p56(lck) activates I-OR independently of CFT R. In lymphocytes from healthy donors, chloride channels could be opened by either intracellular cAMP, p56(lck) or osmotic swelling. In CF lymphocytes , p56(lck) and cell swelling but not cAMP could activate chloride channels. Regulation of I-OR by p56(lck) thus represents an alternative pathway of s timulating membrane chloride conductance that is left intact in cystic fibr osis.