Benedetto, Roberta and Sirianant, Lalida and Pankonien, Ines and Wanitchakool, Podchanart and Ousingsawat, Jiraporn and Cabrita, Ines and Schreiber, Rainer and Amaral, Margarida and Kunzelmann, Karl (2016) Relationship between TMEM16A/anoctamin 1 and LRRC8A. PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY, 468 (10). pp. 1751-1763. ISSN 0031-6768, 1432-2013
Full text not available from this repository. (Request a copy)Abstract
TMEM16A/anoctamin 1/ANO1 and VRAC/LRRC8 are independent chloride channels activated either by increase in intracellular Ca2+ or cell swelling, respectively. In previous studies, we observed overlapping properties for both types of channels. (i) TMEM16A/ANO1 and LRRC8 are inhibited by identical compounds, (ii) the volume-regulated anion channel VRAC requires compartmentalized Ca2+ increase to be fully activated, (iii) anoctamins are activated by cell swelling, (iv) both channels have a role for apoptotic cell death, (v) both channels are possibly located in lipid rafts/caveolae like structures, and (vi) VRAC and anoctamin 1 currents are not additive when each are fully activated. In the present study, we demonstrate in different cell types that loss of LRRC8A expression not only inhibited VRAC, but also attenuated Ca2+ activated Cl- currents. Moreover, expression of LRRC8A enhanced Ca2+ activated Cl- currents, and both LRRC8A and ANO1 could be coimmunoprecipitated. We found that LRRC8A becomes accessible to biotinylation upon exposure to hypotonic bath solution, while membrane capacitance was not enhanced. When intracellular Ca2+ was increased in ANO1-expressing cells, the membrane capacitance was enhanced and increased binding of FM4-64 to the membrane was observed. As this was not seen in cells lacking ANO1 expression, a role of ANO1 for exocytosis was suggested. We propose that ANO1 and LRRC8A are activated in parallel. Thus, ionomycin or purinergic stimulation will not only activate ANO1 but also LRRC8 currents. Cell swelling will not only activate LRRC8/VRAC, but also stimulate ANO1 currents by enhancing compartmentalized Ca2+ increase and/or through swelling induced autocrine release of ATP.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | REGULATED ANION CHANNEL; CELL-VOLUME REGULATION; ASCITES TUMOR-CELLS; SENSITIVE CHLORIDE CHANNELS; OPERATED CA2+ ENTRY; ESSENTIAL COMPONENT; HUMAN OVARIAN; CISPLATIN RESISTANCE; PHOSPHOLIPASE A(2); MOUSE ASTROCYTES; LRRC8A; VRAC; Volume-activated anion channels; Ca2+-activated chloride currents; TMEM16A; Anoctamin 1 |
| Subjects: | 500 Science > 570 Life sciences |
| Divisions: | Biology, Preclinical Medicine > Institut für Physiologie Biology, Preclinical Medicine > Institut für Physiologie > Prof. Dr. Karl Kunzelmann |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 11 Apr 2019 07:59 |
| Last Modified: | 11 Apr 2019 07:59 |
| URI: | https://pred.uni-regensburg.de/id/eprint/4237 |
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