| General information | Literature | Expression | Regulation | Mutation | Interaction |
|
Basic Information |
|
|---|---|
Gene ID | 55107 |
Name | ANO1 |
Synonymous | DOG1|ORAOV2|TAOS2|TMEM16A;anoctamin 1, calcium activated chloride channel;ANO1;anoctamin 1, calcium activated chloride channel |
Definition | anoctamin-1|discovered on gastrointestinal stromal tumors protein 1|oral cancer overexpressed 2|transmembrane protein 16A (eight membrane-spanning domains)|tumor-amplified and overexpressed sequence 2 |
Position | 11q13.3 |
Gene type | protein-coding |
Source | Count: ANO1; 55107 |
|
Sentence |
Abstract |
| augmented Cl(Ca)/TMEM16A channel activity is a major contributor to the changes in electromechanical coupling of pulmonary artery in this model of pulmonary hypertension. | Pulmonary artery smooth muscle cells (PASMCs) are more depolarized and display higher Ca(2+) levels in pulmonary hypertension (PH). Whether the functional properties and expression of Ca(2+)-activated Cl- channels (Cl(Ca)), an important excitatory mechanism in PASMCs, are altered in PH is unknown. The potential role of Cl(Ca) channels in PH was investigated using the monocrotaline (MCT)-induced PH model in the rat. Three weeks postinjection with a single dose of MCT (50 mg/kg ip), the animals developed right ventricular hypertrophy (heart weight measurements) and changes in pulmonary arterial flow (pulse-waved Doppler imaging) that were consistent with increased pulmonary arterial pressure and PH. Whole cell patch experiments revealed an increase in niflumic acid (NFA)-sensitive Ca(2+)-activated Cl(-) current [I(Cl(Ca))] density in PASMCs from large conduit and small intralobar pulmonary arteries of MCT-treated rats vs. aged-matched saline-injected controls. Quantitative RT-PCR and Western blot analysis revealed that the alterations in I(Cl(Ca)) were accompanied by parallel changes in the expression of TMEM16A, a gene recently shown to encode for Cl(Ca) channels. The contraction to serotonin of conduit and intralobar pulmonary arteries from MCT-treated rats exhibited greater sensitivity to nifedipine (1 muM), an l-type Ca(2+) channel blocker, and NFA (30 or 100 muM, with or without 10 muM indomethacin to inhibit cyclooxygenases) or T16A(Inh)-A01 (10 muM), TMEM16A/Cl(Ca) channel inhibitors, than that of control animals. In conclusion, augmented Cl(Ca)/TMEM16A channel activity is a major contributor to the changes in electromechanical coupling of PA in this model of PH. TMEM16A-encoded channels may therefore represent a novel therapeutic target in this disease. |