Calcium-activated chloride currents (CaCCs) are required for epithelial electrolyte and fluid secretion, fertilization, sensory transduction and excitability of neurons and smooth muscle. Defolliculated Xenopus oocytes express a robust CaCC formed by a heterologous group of proteins including transmembrane protein 16A (TMEM16A) and bestrophins. Penetratin, a 17-amino acid peptide, potentiated endogenous oocyte CaCCs by ~50-fold at 10 μM, recorded using a two-electrode voltage clamp. CaCC potentiation was rapid and dose-dependent (EC50 = 3.2 μM). Penetratin-potentiated currents reversed at −18 mV and were dependent on the extracellular divalent cations present, showing positive regulation by Ca2+ and Mg2+ but effective block by Zn2+ (IC50 = 5.9 μM). Extracellular Cd2+, Cu2+ and Ba2+ resulted in bimodal responses: CaCC inhibition at low but potentiation at high concentrations. Intracellular BAPTA injection, which prevents activation of CaCCs, and the Cl− channel blockers niflumic acid and DIDS significantly reduced potentiation. In contrast, the K+ channel blockers Cs+, TEA, tertiapin-Q and halothane had no significant effect. This pharmacological profile is consistent with penetratin potentiation of zinc-sensitive CaCCs that are activated by influx of extracellular Ca2+. These findings may stimulate basic research on CaCCs in native cells and may lead to development of novel therapeutics targeting disorders caused by insufficient chloride secretion.
The Journal of Membrane Biology – Springer Journals
Published: Mar 27, 2011
It’s your single place to instantly
discover and read the research
that matters to you.
Enjoy affordable access to
over 18 million articles from more than
15,000 peer-reviewed journals.
All for just $49/month
Query the DeepDyve database, plus search all of PubMed and Google Scholar seamlessly
Save any article or search result from DeepDyve, PubMed, and Google Scholar... all in one place.
Get unlimited, online access to over 18 million full-text articles from more than 15,000 scientific journals.
Read from thousands of the leading scholarly journals from SpringerNature, Elsevier, Wiley-Blackwell, Oxford University Press and more.
All the latest content is available, no embargo periods.
“Hi guys, I cannot tell you how much I love this resource. Incredible. I really believe you've hit the nail on the head with this site in regards to solving the research-purchase issue.”Daniel C.
“Whoa! It’s like Spotify but for academic articles.”@Phil_Robichaud
“I must say, @deepdyve is a fabulous solution to the independent researcher's problem of #access to #information.”@deepthiw
“My last article couldn't be possible without the platform @deepdyve that makes journal papers cheaper.”@JoseServera