Activation of the TASK-2 channel after cell swelling is dependent on tyrosine phosphorylation

American Journal of Physiology. Cell Physiology
Signe Skyum KirkegaardElse Kay Hoffmann

Abstract

The swelling-activated K(+) currents (I(K,vol)) in Ehrlich ascites tumor cells (EATC) has been reported to be through the two-pore domain (K(2p)), TWIK-related acid-sensitive K(+) channel 2 (TASK-2). The regulatory volume decrease (RVD), following hypotonic exposure in EATC, is rate limited by I(K,vol) indicating that inhibition of RVD reflects inhibition of TASK-2. We find that in EATC the tyrosine kinase inhibitor genistein inhibits RVD by 90%, and that the tyrosine phosphatase inhibitor monoperoxo(picolinato)-oxo-vanadate(V) [mpV(pic)] shifted the volume set point for inactivation of the channel to a lower cell volume. Swelling-activated K(+) efflux was impaired by genistein and the Src kinase family inhibitor 4-amino-5-(4-chloro-phenyl)-7-(t-butyl)pyrazolo[3,4-d]pyrimidine (PP2) and enhanced by the tyrosine phosphatase inhibitor mpV(pic). With the use of the TASK-2 inhibitor clofilium, it is demonstrated that mpV(pic) increased the volume-sensitive part of the K(+) efflux 1.3 times. To exclude K(+) efflux via a KCl cotransporter, cellular Cl(-) was substituted with NO(3)(-). Also under these conditions K(+) efflux was completely blocked by genistein. Thus tyrosine kinases seem to be involved in the activation of the volume-...Continue Reading

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Citations

Jul 3, 2013·Pflügers Archiv : European journal of physiology·Carolina AñazcoMaría Isabel Niemeyer
Sep 30, 2010·Acta Physiologica·E K Hoffmann, S F Pedersen
Jan 24, 2014·PLoS Genetics·Simon PerathonerMatthew P Harris
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Oct 16, 2014·Pflügers Archiv : European journal of physiology·Karen I López-CayuqueoL Pablo Cid
Jun 22, 2016·Molecular Neurobiology·Yu-Jie LaiGuo-Jun Chen
Jul 1, 2016·Molecular Pharmacology·Herminia Pasantes-Morales
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Nov 1, 2012·Seminars in Immunopathology·M F BassendineR D G Neely
Feb 11, 2011·American Journal of Physiology. Cell Physiology·Joo Hyun NamSung Joon Kim
Mar 15, 2013·American Journal of Physiology. Cell Physiology·Jacob Bak HolmIan Henry Lambert

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