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, 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
A
Department for Physiology, University of Tübingen, Tübingen, Germany. alepplew@uni-tuebingen.de
Wieland
U
U
Laun
T
T
Heil
L
L
Stern
M
M
Lang
F
F
D018118:Chloride Channels / Q000378:metabolism*; D000242:Cyclic AMP / Q000378:metabolism; D003550:Cystic Fibrosis / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000378:metabolism; D004594:Electrophysiology; D006801:Humans; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / Q000378:metabolism*; D008214:Lymphocytes / Q000201:enzymology* / Q000378:metabolism / Q000502:physiology; D009994:Osmolar Concentration; D019061:src-Family Kinases / Q000378:metabolism
C505032:CFTR protein, human; D018118:Chloride Channels; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D000242:Cyclic AMP; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D019061:src-Family Kinases