TRPV4 heats ups ANO1-dependent exocrine gland fluid secretion

[Speaker] Sandra Derouiche:1
[Co-author] Yasunori Takayama:1, Masataka Murakami:1, Makoto Tominaga:1
1:Okazaki Institute for Integrative Bioscience, National Institute for Physiological Sciences, Japan

Several ion channels and transporters regulate fluid secretion in salivary and lacrimal glands. In salivary glands, the major anion channel involved in fluid secretion is the calcium-activated chloride channel anoctamin 1 (ANO1). Several members of the transient receptor potential (TRP) channel superfamily regulate ANO1 activity. Here, we report a functional interaction between thermosensitive TRPV4 and ANO1 in acinar cells isolated from mouse salivary and lacrimal glands. TRPV4 activation induced chloride currents and shrinkage of acinar cells by increase in intracellular calcium concentrations. The chloride currents evoked by a TRPV4-specific activator (GSK1016790A) were identified as ANO1-mediated currents. Moreover, TRPV4 activation by an IP3-dependent mechanism was found to contribute to the muscarinic pathway of fluid secretion. Muscarinic stimulation of saliva and tear secretion was downregulated in both TRPV4-deficient mice and in acinar cells treated with a TRPV4-specific antagonist (HC-067047). Furthermore, the temperature dependence of muscarinic salivation was shown to depend mainly on TRPV4. Our results suggest that TRPV4 interacts with IP3 receptors and ANO1 to regulate the muscarinic pathway that mediates salivation and lacrimation. We propose that interactions between TRP channels and anoctamins may occur in all tissues that perform secretory functions, and that regulation of fluid secretion through the modulation of TRP channel activity could offer new strategies for treating exocrine gland diseases.

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