AE4 is an anion exchanger known to counter transport Cl− and HCO3− across secretory cell membranes. Peña-Münzenmayer et al. show that AE4 is an electroneutral exchanger and that it also transports monovalent cations in the same direction as HCO3−.

The solute carrier family 26 () gene family encodes at least 10 different anion exchangers. SLC26 member 6 (SLC26A6 or CFEX/PAT-1) and the cystic fibrosis transmembrane conductance regulator (CFTR) co-localize to the apical membrane of pancreatic duct cells, where they act in concert to drive HCO and fluid secretion. In contrast, in the small intestine, SLC26A6 serves as the major pathway for oxalate secretion. However, little is known about the function of Slc26a6 in murine salivary glands. Here, RNA sequencing-based transcriptional profiling and Western blots revealed that is highly expressed in mouse submandibular and sublingual salivary glands. Slc26a6 localized to the apical membrane of salivary gland acinar cells with no detectable immunostaining in the ducts. CHO-K1 cells transfected with mouse exchanged Cl for oxalate and HCO, whereas two other anion exchangers known to be expressed in salivary gland acinar cells, Slc4a4 and Slc4a9, mediated little, if any, Cl/oxalate exchange. Of note, both Cl/oxalate exchange and Cl/HCO exchange were significantly reduced in acinar cells isolated from the submandibular glands of mice. Oxalate secretion in submandibular saliva also decreased significantly in mice, but HCO secretion was unaffected. Taken together, our findings indicate that Slc26a6 is located at the apical membrane of salivary gland acinar cells, where it mediates Cl/oxalate exchange and plays a critical role in the secretion of oxalate into saliva.

This randomized, active-controlled, double-blind, prospective clinical trial evaluated the anesthetic efficacy of 2% lidocaine with 1:200,000 epinephrine versus an admixture of 2% lidocaine with 1:200,000 epinephrine and 1 mL of 4 mg dexamethasone (Twin mix) for inferior alveolar nerve blocks (IANBs) in patients with symptomatic irreversible pulpitis (SIP) of the mandibular molars. Seventy-eight patients with SIP of mandibular molars were randomly allocated to the 2 groups of 39 subjects. All patients were required to have profound lip numbness within 10 minutes of local anesthetic deposition. The efficacy of pulpal anesthesia was confirmed by absence of pain or mild pain (Heft-Parker visual analogue scale ≤54 mm) during access cavity preparation and placement of glide path files. The collected data were subjected to independent t test, chi-square test, and Fisher exact test using SPSS software version 20.0 at a significance level of 0.05. IANB success rates for the lidocaine group and the Twin mix group was 66% and 68% respectively, which was not a statistically significant difference (p > .05). This study demonstrated that the anesthetic efficacy of Twin mix was equivalent to 2% lidocaine for IANBs in teeth with SIP.

The Human Embryonic Kidney 293 cell line (HEK‐293) readily lends itself to genetic manipulation and is a common tool for biologists to overexpress proteins of interest and study their function and molecular regulation. Although these cells have some limitations, such as an inability to form resistive monolayers necessary for studying transepithelial ion transport, they are nevertheless valuable in studying individual epithelial ion transporters. We report the use of HEK‐293 cells to study the cystic fibrosis transmembrane conductance regulator (CFTR) Cl− channel. While HEK‐293 cells endogenously express mRNA for the Cl− channels, ClC‐2 and TMEM16A, they neither express CFTR mRNA nor protein. Therefore, we stably transfected HEK‐293 cells with EGFP‐CFTR (HEK‐CFTR) and demonstrated CFTR function by measuring forskolin‐stimulated iodide efflux. This efflux was inhibited by CFTRinh172, and the protein kinase A inhibitor H89, but not by Ca2+ chelation. In contrast to intestinal epithelia, forskolin stimulation does not increase surface CFTR expression and does not require intact microtubules in HEK‐CFTR. To investigate the role of an endogenous GαS‐coupled receptor, we examined the bile acid receptor, TGR5. Although HEK‐CFTR cells express TGR5, the potent TGR5 agonist lithocholic acid (LCA; 5–500 μmol/L) did not activate CFTR. Furthermore, forskolin, but not LCA, increased [cAMP]i in HEK‐CFTR suggesting that endogenous TGR5 may not be functionally linked to GαS. However, LCA did increase [Ca2+]i and interestingly, abolished forskolin‐stimulated iodide efflux. Thus, we propose that the stable HEK‐CFTR cell line is a useful model to study the multiple signaling pathways that regulate CFTR.