dc.creator | Sun, Yuyang | |
dc.creator | Birnbaumer, Lutz | |
dc.creator | Singh, Brij B. | |
dc.date.accessioned | 2018-03-05T19:27:15Z | |
dc.date.accessioned | 2018-11-06T11:35:33Z | |
dc.date.available | 2018-03-05T19:27:15Z | |
dc.date.available | 2018-11-06T11:35:33Z | |
dc.date.created | 2018-03-05T19:27:15Z | |
dc.date.issued | 2015-11 | |
dc.identifier | Sun, Yuyang; Birnbaumer, Lutz; Singh, Brij B.; TRPC1 regulates calcium-activated chloride channels in salivary gland cells; Wiley-liss, Div John Wiley & Sons Inc; Journal of Cellular Physiology; 230; 11; 11-2015; 2848-2856 | |
dc.identifier | 0021-9541 | |
dc.identifier | http://hdl.handle.net/11336/37875 | |
dc.identifier | CONICET Digital | |
dc.identifier | CONICET | |
dc.identifier.uri | http://repositorioslatinoamericanos.uchile.cl/handle/2250/1855313 | |
dc.description.abstract | Calcium-activated chloride channel (CaCC) plays an important role in modulating epithelial secretion. It has been suggested that in salivary tissues, sustained fluid secretion is dependent on Ca2+ influx that activates ion channels such as CaCC to initiate Cl- efflux. However direct evidence as well as the molecular identity of the Ca2+ channel responsible for activating CaCC in salivary tissues is not yet identified. Here we provide evidence that in human salivary cells, an outward rectifying Cl- current was activated by increasing [Ca2+]i, which was inhibited by the addition of pharmacological agents niflumic acid (NFA), an antagonist of CaCC, or T16Ainh-A01, a specific TMEM16a inhibitor. Addition of thapsigargin (Tg), that induces store-depletion and activates TRPC1-mediated Ca2+ entry, potentiated the Cl- current, which was inhibited by the addition of a non-specific TRPC channel blocker SKF96365 or removal of external Ca2+. Stimulation with Tg also increased plasma membrane expression of TMEM16a protein, which was also dependent on Ca2+ entry. Importantly, in salivary cells, TRPC1 silencing, but not that of TRPC3, inhibited CaCC especially upon store depletion. Moreover, primary acinar cells isolated from submandibular gland also showed outward rectifying Cl- currents upon increasing [Ca2+]i. These Cl- currents were again potentiated with the addition of Tg, but inhibited in the presence of T16Ainh-A01. Finally, acinar cells isolated from the submandibular glands of TRPC1 knockout mice showed significant inhibition of the outward Cl- currents without decreasing TMEM16a expression. Together the data suggests that Ca2+ entry via the TRPC1 channels is essential for the activation of CaCC. | |
dc.language | eng | |
dc.publisher | Wiley-liss, Div John Wiley & Sons Inc | |
dc.relation | info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1002/jcp.25017 | |
dc.relation | info:eu-repo/semantics/altIdentifier/url/http://onlinelibrary.wiley.com/doi/10.1002/jcp.25017/abstract | |
dc.rights | https://creativecommons.org/licenses/by-nc-sa/2.5/ar/ | |
dc.rights | info:eu-repo/semantics/openAccess | |
dc.subject | TMEM6a | |
dc.subject | TRPC1 | |
dc.subject | salivary gland | |
dc.subject | Ca activated chloride channel | |
dc.title | TRPC1 regulates calcium-activated chloride channels in salivary gland cells | |
dc.type | Artículos de revistas | |
dc.type | Artículos de revistas | |
dc.type | Artículos de revistas | |