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

ALBECHT LEPPLE-WIENHUES^*,12, ULRICH WIELAND^*,1, TILMANN LAUN, LUZIA HEIL, MARTIN STERN and FLORIAN LANG

Department for
^* Physiology and of
Pediatric Medicine, University of Tübingen, Tübingen, Germany

²Correspondence: Physiologisches Institut der Universität Tübingen, Gmelinstr. 5, D-72076 Tübingen, Germany. E-mail: alepplew{at}uni-tuebingen.de

Defective activation of chloride channels is a hallmark of cystic fibrosis (CF). Recently we have described activation of a volume-sensitive, outwardly rectifying chloride conductance (I_OR) through the src-like tyrosine kinase p56^lck. Here we show that p56^lck activates I_OR independently of CFTR. 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 stimulating membrane chloride conductance that is left intact in cystic fibrosis.—Lepple-Wienhues, A., Wieland, U., Laun, T., Heil, L., Stern, M., Lang, F. A src-like kinase activates outwardly rectifying chloride channels in CFTR-defective lymphocytes.

Key Words: cystic fibrosis • tyrosine kinase • human lymphocytes • cyclic adenosine monophosphate • cell volume

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