Proceedings of The Physiological Society

Europhysiology 2018 (London, UK) (2018) Proc Physiol Soc 41, PCA118

Poster Communications

ATP-induced constitutive mucus secretion requires TMEM16A for mucus secretion in large intestine

I. Cabrita1, R. Benedetto1, R. Schreiber1, K. Kunzelmann1

1. Institut für Physiologie, Universität Regensburg, Regensburg, Germany.

TMEM16A is a calcium activated chloride channel found in the intestine and has been associated with goblet cell metaplasia. Here we report for the first time that TMEM16A is essential for basal secretion of intestinal mucus. Intestinal epithelial knockout of TMEM16A leads to accumulation of mucus in intestinal goblet cells. Acute ATP-induced mucus secretion by colonic goblet cells is strongly compromised in the absence of TMEM16A and requires apical calcium. In contrast cholinergic mucus secretion due to compound exocytosis is independent of TMEM16A. The data demonstrate a previously unrecognized role of TMEM16A for membrane exocytosis in HEK293 cells overexpressing TMEM16A and describe a novel ATP-driven pathway for intestinal mucus secretion. We conclude that ATP-dependent constitutive mucus secretion in the intestine requires TMEM16A and apical calcium influx. The results provide the basis for a completely novel therapeutic approach for the treatment of intestinal mucus-dependent diseases.

Where applicable, experiments conform with Society ethical requirements