Inhibition of CFTR channels by a peptide toxin of scorpion venom

American Journal of Physiology. Cell Physiology
Matthew D FullerN A McCarty

Abstract

Peptide toxins have been valuable probes in efforts to identify amino acid residues that line the permeation pathway of cation-selective channels. However, no peptide toxins have been identified that interact with known anion-selective channels such as the cystic fibrosis transmembrane conductance regulator (CFTR). CFTR channels are expressed in epithelial cells and are associated with several genetic disorders, including cystic fibrosis and polycystic kidney disease. Several organic inhibitors have been used to investigate the structure of the Cl- permeation pathway in CFTR. However, investigations of the wider cytoplasmic vestibule have been hindered by the lack of a high-affinity blocker that interacts with residues in this area. In this study we show that venom of the scorpion Leiurus quinquestriatus hebraeus reversibly inhibits CFTR, in a voltage-independent manner, by decreasing single-channel mean burst duration and open probability only when applied to the cytoplasmic surface of phosphorylated channels. Venom was able to decrease burst duration and open probability even when CFTR channels were locked open by treatment with either vanadate or adenosine 5'-(beta,gamma-imido)triphosphate, and block was strengthened on redu...Continue Reading

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Citations

Nov 30, 2005·Cellular and Molecular Life Sciences : CMLS·M SuzukiT Iwamoto
Jul 4, 2009·The Journal of Biological Chemistry·Christopher H ThompsonNael A McCarty
May 31, 2008·American Journal of Physiology. Gastrointestinal and Liver Physiology·Hui Fang BaoDouglas C Eaton
Jul 12, 2013·Journal of Toxicology·Bennasr HmedZeghal Khaled Mounir
Jun 23, 2010·Proceedings of the National Academy of Sciences of the United States of America·Staci P CohenNael A McCarty
Apr 6, 2006·The Journal of Membrane Biology·C H ThompsonN A McCarty
Feb 14, 2006·Progress in Retinal and Eye Research·Geoffrey B Arden, Paul A Constable
Sep 27, 2005·Biophysical Journal·Matthew D FullerNael A McCarty
Jul 11, 2013·PloS One·Laura L Valdez-VelázquezLourival D Possani
Dec 1, 2008·Journal of Cardiovascular Translational Research·Sabu Thomas, Edward O McFalls
Sep 25, 2008·Nature Clinical Practice. Nephrology·Visith Sitprija
Feb 21, 2006·The Journal of Pharmacology and Experimental Therapeutics·Tingcun ZhaoRichard P Shannon
Aug 25, 2009·BioDrugs : Clinical Immunotherapeutics, Biopharmaceuticals and Gene Therapy·Hongyu Li, David N Sheppard
Dec 14, 2011·Pflügers Archiv : European journal of physiology·Guiying CuiNael A McCarty
Feb 5, 2008·The Journal of Experimental Biology·Staci A Padove CohenNael A McCarty

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