Roles of CLCA and CFTR in electrolyte re-absorption from rat saliva.

A molecular basis for Cl- re-absorption has not been well-characterized in salivary ductal cells. Previously, we found strong expression of a rat homologue proposed to be Ca2+-dependent Cl- channels (rCLCA) in the intralobular ducts of the rat submandibular gland. To address the question as to whether rCLCA and cystic fibrosis transmembrane conductance regulator (CFTR) are involved in Cl- re-absorption, we evaluated the electrolyte content of saliva from glands pre-treated with a small interfering RNA (siRNA). Retrograde injection into a given submandibular duct of an siRNA designed to knock down either rCLCA or CFTR reduced the expression of each of the proteins. rCLCA and CFTR siRNAs significantly increased Cl- concentration in the final saliva during pilocarpine stimulation. These results represent the first in vivo evidence for a physiological significance of rCLCA, along with CFTR, in transepithelial Cl- transport in the ductal system of the rat submandibular gland.