Calcium-activated chloride channel protein 1 (TMEM16A (also known as ANO1))

Calcium-activated chloride channels are membrane proteins crucial for epithelial Cl^− and water secretion. The principal channel in the intestinal epithelium is Anoctamin 1 (TMEM16A), which responds to increases in intracellular Ca^2+ by allowing chloride ions to exit epithelial cells into the intestinal lumen. This drives water movement by osmosis, aiding in hydration of the intestinal tract and mucus layer. TMEM16A is highly expressed in the intestine (notably in epithelial and interstitial cells of Cajal), as well as in airway, sensory, and other tissues. Dysregulation contributes to diseases such as secretory diarrhea (overactivation) and cystic fibrosis (potentially beneficial compensation for defective CFTR). TMEM16A is a validated therapeutic target for both inhibitors (to treat secretory diarrhea) and activators (as an alternative therapeutic approach in cystic fibrosis).

Other names

Anoctamin 1 (ANO1)Transmembrane protein 16A (TMEM16A)Calcium-activated chloride channel 1 (CaCC1)Intestinal calcium-activated chloride channel (informal, tissue-specific context)

Inhibitors: Block Ca^2+-activated gating of the channel, preventing anion (Cl^−) flux and thereby reducing intestinal fluid secretion. Activators: Elevate cytoplasmic Ca^2+ or directly activate the channel to promote chloride and fluid secretion, useful in cystic fibrosis.