Abstract
Calcium-activated chloride channels (CaCCs) play important roles in a multitude of physiological processes, and in many cells types, TMEM16A was identified as the molecular basis of CaCC. Abnormal CaCC function has been implicated in variety of diseases, which reinforces the need for modulators of CaCCs/TMEM16A. However, there are few specific, clinical modulators of CaCCs. Here, we identified a potent novel activator of TMEM16A from a bank of traditional Chinese medicines (TCM) and explored its mechanism of activation by laser confocal scanning microscopy and patch clamping. Fluorescence data demonstrated that among the 36 tested TCM medicines, one compound, cinnamaldehyde (CA), can activate the TMEM16A channel in a dose-dependent manner. To determine the mechanism by which CA activates the TMEM16A channel, we performed an excised patch clamp experiment and measured the intracellular calcium concentration in fluorescence experiments. Our data show that CA activates TMEM16A channels by elevating the intracellular concentrations of calcium ions. The results of the whole-cell patch clamping showed that CA dose-dependently activates these channels, with an EC50 of 9.73 ± 5.64µM at + 80mV, and prolongs the deactivation of TMEM16A. Finally, we found that CA can strengthen contractions of the ileum in guinea pigs by activating TMEM16A. The results demonstrate that CA is a novel, natural activator of TMEM16A.
Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
