Dynamic modulation of ANO1/TMEM16A HCO3(-) permeability by Ca2+/calmodulin
Jinsei Jung1, Joo Hyun Nam, Hyun Woo Park
1Department of Pharmacology, Brain Korea 21 Project for Medical Sciences, Yonsei University College of Medicine, Seoul 120-752, Korea.
Summary
Anoctamin 1 (ANO1) channels dynamically regulate bicarbonate (HCO3-) secretion. Calcium and calmodulin binding increases ANO1
Area of Science:
- Cellular physiology
- Ion channel function
- Epithelial transport
Background:
- Anoctamin 1 (ANO1)/transmembrane protein 16A (TMEM16A) is a calcium-activated anion channel.
- ANO1 is implicated in HCO3- secretion in epithelial cells.
Purpose of the Study:
- To investigate the dynamic regulation of ANO1 anion selectivity by Ca2+/calmodulin.
- To elucidate the role of ANO1 in HCO3- transport.
Main Methods:
- Whole-cell current measurements in HEK 293T cells.
- Excised patch-clamp electrophysiology.
- Biochemical assays to confirm protein interactions.
Main Results:
- ANO1 exhibits increased HCO3- permeability at high intracellular Ca2+ concentrations ([Ca2+]i).
- This regulation requires cytosolic factors, specifically calmodulin, which directly binds ANO1.
- Increased HCO3- permeability was observed in mouse submandibular gland acinar cells.
Conclusions:
- ANO1 anion selectivity is dynamically modulated by Ca2+/calmodulin.
- ANO1 plays a significant role in cellular and transepithelial HCO3- secretion.
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