Sirianant, Lalida and Ousingsawat, Jiraporn and Wanitchakool, Podchanart and Schreiber, Rainer and Kunzelmann, Karl (2016) Cellular volume regulation by anoctamin 6: Ca2+, phospholipase A2 and osmosensing. PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY, 468 (2). pp. 335-349. ISSN 0031-6768, 1432-2013
Full text not available from this repository. (Request a copy)Abstract
During cell swelling, Cl- channels are activated to lower intracellular Cl- concentrations and to reduce cell volume, a process termed regulatory volume decrease (RVD). We show that anoctamin 6 (ANO6; TMEM16F) produces volume-regulated anion currents and controls cell volume in four unrelated cell types. Volume regulation is compromised in freshly isolated intestinal epithelial cells from Ano6-/- mice and also in lymphocytes from a patient lacking expression of ANO6. Ca2+ influx is activated and thus ANO6 is stimulated during cell swelling by local Ca2+ increase probably in functional nanodomains near the plasma membrane. This leads to stimulation of phospholipase A(2) (PLA(2)) and generation of plasma membrane lysophospholipids, which activates ANO6. Direct application of lysophospholipids also activates an anion current that is inhibited by typical ANO6 blocker. An increase in intracellular Ca2+ supports activation of ANO6, but is not required when PLA(2) is fully activated, while re-addition of arachidonic acid completely blocked ANO6. Moreover, ANO6 is activated by low intracellular Cl- concentrations and may therefore operate as a cellular osmosensor. High intracellular Cl- concentration inhibits ANO6 and activation by PLA(2). Taken together, ANO6 supports volume regulation and volume activation of anion currents by action as a Cl- channel or by scrambling membrane phospholipids. Thereby, it may support the function of LRRC8 proteins.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | CA2+-ACTIVATED CL-CHANNEL; ASCITES TUMOR-CELLS; ANION CHANNELS; ESSENTIAL COMPONENT; ENDOTHELIAL-CELLS; IONIC-STRENGTH; HEK293 CELLS; A(2); ACTIVATION; TMEM16F; TMEM16F; Anoctamin 6; Volume regulation; Regulatory volume decrease; RVD; Volume-regulated anion channel; VRAC; Apoptosis |
| Subjects: | 500 Science > 570 Life sciences |
| Divisions: | Biology, Preclinical Medicine > Institut für Physiologie > Prof. Dr. Karl Kunzelmann |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 14 Mar 2019 11:15 |
| Last Modified: | 14 Mar 2019 11:15 |
| URI: | https://pred.uni-regensburg.de/id/eprint/2502 |
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