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© The Rockefeller University Press, 0021-9525/1998//281 $5.00
The Journal of Cell Biology, Volume 141, Number 1, , 1998 281-286

Regular Articles

The Tyrosine Kinase p56lck Mediates Activation of Swelling-induced Chloride Channels in Lymphocytes



Albrecht Lepple-Wienhues, Ildikò Szabò, Tilmann Laun, Nubia Kristen Kaba, Erich Gulbins, and Florian Lang

Department of Physiology, University of Tübingen, D-72076 Tübingen, Germany

Osmotic cell swelling activates Cl– channels to achieve anion efflux. In this study, we find that both the tyrosine kinase inhibitor herbimycin A and genetic knockout of p56lck, a src-like tyrosine kinase, block regulatory volume decrease (RVD) in a human T cell line. Activation of a swelling-activated chloride current (ICl–swell) by osmotic swelling in whole-cell patch-clamp experiments is blocked by herbimycin A and lavendustin. Osmotic activation of ICl–swell is defective in p56lck-deficient cells. Retransfection of p56lck restores osmotic current activation. Furthermore, tyrosine kinase activity is sufficient for activation of ICl–swell. Addition of purified p56lck to excised patches activates an outwardly rectifying chloride channel with 31 pS unitary conductance. Purified p56lck washed into the cytoplasm activates ICl–swell in native and p56lck-deficient cells even when hypotonic intracellular solutions lead to cell shrinkage. When whole-cell currents are activated either by swelling or by p56lck, slow single-channel gating events can be observed revealing a unitary conductance of 25–28 pS. In accordance with our patch-clamp data, osmotic swelling increases activity of immunoprecipitated p56lck. We conclude that osmotic swelling activates ICl–swell in lymphocytes via the tyrosine kinase p56lck.

Abbreviations used in this paper: RVD, regulatory volume decrease; ICl, chloride current; ICl–swell, swelling-activated chloride current; CFTR, cystic fibrosis transmembrane conductance regulator; DIDS, diisothiocyanato-2-2-stilbenesulfonic acid.

This work was in part funded by Deutsche Forschungsgemeinschaft Le 792/3-1, La 315/4-3, and Bundesministerium für Bildung, Wissenschaft, Forschung und Technologie/Interdisziplinäres Klinisches Forschungszentrum 01KS9605. I. Szabò is grateful for a European Molecular Biology Organization fellowship.

E. Gulbins and F. Lang contributed equally to this work.


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