Characterization of the effects of Cl?/sup> channel modulators on TMEM16A and bestrophin-1 Ca2+ activated Cl?/sup> channels

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• 作者：Yani Liu ; Huiran Zhang ; Dongyang Huang…
• 关键词：Ca2+ activated Cl?channels (CaCCs) ; TMEM16A ; Bestrophin ; 1 ; Inhibitor ; CHO cells ; Patch clamp
• 刊名：Pfl篓鹿gers Archiv - European Journal of Physiology
• 出版年：2015
• 出版时间：July 2015
• 年：2015
• 卷：467
• 期：7
• 页码：1417-1430
• 全文大小：1,455 KB
• 参考文献：1.Barro-Soria R, Aldehni F, Almaca J, Witzgall R, Schreiber R, Kunzelmann K (2010) ER-localized bestrophin 1 activates Ca2+-dependent ion channels TMEM16A and SK4 possibly by acting as a counterion channel. Pflugers Arch 459(3):485-97. doi:10.-007/?s00424-009-0745-0 PubMed View Article
  2.Boudes M, Sar C, Menigoz A, Hilaire C, Pequignot MO, Kozlenkov A, Marmorstein A, Carroll P, Valmier J, Scamps F (2009) Best1 is a gene regulated by nerve injury and required for Ca2+-activated Cl?/sup> current expression in axotomized sensory neurons. J Neurosci 29(32):10063-0071. doi:10.-523/?JNEUROSCI.-312-09.-009 PubMed Central PubMed View Article
  3.Bradley E, Fedigan S, Webb T, Hollywood MA, Thornbury KD, McHale NG, Sergeant GP (2014) Pharmacological characterization of TMEM16A currents. Channels (Austin) 8 (3). doi:28065
  4.Caputo A, Caci E, Ferrera L, Pedemonte N, Barsanti C, Sondo E, Pfeffer U, Ravazzolo R, Zegarra-Moran O, Galietta LJ (2008) TMEM16A, a membrane protein associated with calcium-dependent chloride channel activity. Science 322(5901):590-94. doi:10.-126/?science.-163518 PubMed View Article
  5.Cho H, Yang YD, Lee J, Lee B, Kim T, Jang Y, Back SK, Na HS, Harfe BD, Wang F, Raouf R, Wood JN, Oh U (2012) The calcium-activated chloride channel anoctamin 1 acts as a heat sensor in nociceptive neurons. Nat Neurosci 15(7):1015-021. doi:10.-038/?nn.-111 PubMed View Article
  6.De La Fuente R, Namkung W, Mills A, Verkman AS (2008) Small-molecule screen identifies inhibitors of a human intestinal calcium-activated chloride channel. Mol Pharmacol 73(3):758-68. doi:10.-124/?mol.-07.-43208 View Article
  7.Dibattista M, Amjad A, Maurya DK, Sagheddu C, Montani G, Tirindelli R, Menini A (2012) Calcium-activated chloride channels in the apical region of mouse vomeronasal sensory neurons. J Gen Physiol 140(1):3-5. doi:10.-085/?jgp.-01210780 PubMed Central PubMed View Article
  8.Ferrera L, Caputo A, Ubby I, Bussani E, Zegarra-Moran O, Ravazzolo R, Pagani F, Galietta LJ (2009) Regulation of TMEM16A chloride channel properties by alternative splicing. J Biol Chem 284(48):33360-3368. doi:10.-074/?jbc.?M109.-46607 PubMed Central PubMed View Article
  9.Francois A, Grauso M, Demondion E, Bozzolan F, Debernard S, Lucas P (2012) Bestrophin-encoded Ca(2)(+)-activated Cl(? channels underlie a current with properties similar to the native current in the moth Spodoptera littoralis olfactory receptor neurons. PLoS One 7(12):e52691. doi:10.-371/?journal.?pone.-052691 PubMed Central PubMed View Article
  10.Gomez NM, Tamm ER, Straubeta O (2013) Role of bestrophin-1 in store-operated calcium entry in retinal pigment epithelium. Pflugers Arch 465(4):481-95. doi:10.-007/?s00424-012-1181-0 PubMed View Article
  11.Greenwood IA, Large WA (1998) Properties of a Cl?/sup> current activated by cell swelling in rabbit portal vein vascular smooth muscle cells. Am J Physiol 275(5 Pt 2):H1524–H1532PubMed
  12.Greenwood IA, Leblanc N (2007) Overlapping pharmacology of Ca2+-activated Cl?/sup> and K+ channels. Trends Pharmacol Sci 28(1):1-. doi:10.-016/?j.?tips.-006.-1.-04 PubMed View Article
  13.Habjan S, Vandenberg RJ (2009) Modulation of glutamate and glycine transporters by niflumic, flufenamic and mefenamic acids. Neurochem Res 34(10):1738-747. doi:10.-007/?s11064-009-9983-y PubMed View Article
  14.Hartzell C, Putzier I, Arreola J (2005) Calcium-activated chloride channels. Annu Rev Physiol 67:719-58. doi:10.-146/?annurev.?physiol.-7.-32003.-54341 PubMed View Article
  15.Hartzell C, Qu Z, Putzier I, Artinian L, Chien LT, Cui Y (2005) Looking chloride channels straight in the eye: bestrophins, lipofuscinosis, and retinal degeneration. Physiology (Bethesda) 20:292-02. doi:10.-152/?physiol.-0021.-005 View Article
  16.Hartzell HC, Qu Z, Yu K, Xiao Q, Chien LT (2008) Molecular physiology of bestrophins: multifunctional membrane proteins linked to best disease and other retinopathies. Physiol Rev 88(2):639-72. doi:10.-152/?physrev.-0022.-007 PubMed View Article
  17.Jeon JH, Paik SS, Chun MH, Oh U, Kim IB (2013) Presynaptic localization and possible function of calcium-activated chloride channel anoctamin 1 in the mammalian retina. PLoS One 8(6):e67989. doi:10.-371/?journal.?pone.-067989 PubMed Central PubMed View Article
  18.Jin X, Shah S, Liu Y, Zhang H, Lees M, Fu Z, Lippiat JD, Beech DJ, Sivaprasadarao A, Baldwin SA, Gamper N (2013) Activation of the Cl?/sup> channel ANO1 by localized calcium signals in nociceptive sensory neurons requires coupling with the IP3 receptor. Sci Signal 6(290):ra73. doi:10.-126/?scisignal.-004184 PubMed Central PubMed View Article
  19.Kunzelmann K, Kongsuphol P, Aldehni F, Tian Y, Ousingsawat J, Warth R, Schreiber R (2009) Bestrophin and TMEM16-Ca(2+) activated Cl(? channels with different functions. Cell Calcium 46(4):233-41. doi:10.-016/?j.?ceca.-009.-9.-03 PubMed View Article
  20.Kunzelmann K, Kongsuphol P,
• 作者单位：Yani Liu (1)
  Huiran Zhang (1)
  Dongyang Huang (1)
  Jinlong Qi (1)
  Jiaxi Xu (1)
  Haixia Gao (1)
  Xiaona Du (1)
  Nikita Gamper (1) (2)
  Hailin Zhang (1)
  
  1. Key Laboratory of Neural and Vascular Biology, Ministry of Education; Key Laboratory of New Drug Pharmacology and Toxicology, Hebei Province; Department of Pharmacology, Hebei Medical University, Shijizhuang, Heibei, China
  2. School of Biomedical Sciences, Faculty of Biological Sciences, University of Leeds, Leeds, UK
  
• 刊物主题：Human Physiology;
• 出版者：Springer Berlin Heidelberg
• ISSN：1432-2013

文摘

The Ca2+ activated Cl?/sup> channels (CaCCs) play a multitude of important physiological functions. A number of candidate proteins have been proposed to form CaCC, but only two families, the bestrophins and the TMEM16 proteins, recapitulate the properties of native CaCC in expression systems. Studies of endogenous CaCCs are hindered by the lack of specific pharmacology as most Cl?/sup> channel modulators lack selectivity and a systematic comparison of the effects of these modulators on TMEM16A and bestrophin is missing. In the present study, we studied seven Cl?/sup> channel inhibitors: niflumic acid (NFA), NPPB, flufenamic acid (FFA), DIDS, tannic acid, CaCCinh-A01 and T16Ainh-A01 for their effects on TMEM16A and bestrophin-1 (Best1) stably expressed in CHO (Chinese hamster ovary) cells using patch clamp technique. Among seven inhibitors studied, NFA showed highest selectivity for TMEM16A (IC50 of 7.40?±-.95?μM) over Best1 (IC50 of 102.19?±-5.05?μM). In contrast, DIDS displayed a reverse selectivity inhibiting Best1 with IC50 of 3.93?±-.73?μM and TMEM16A with IC50 of 548.86?±-5.57?μM. CaCCinh-A01 was the most efficacious blocker for both TMEM16A and Best1 channels. T16Ainh-A01 partially inhibited TMEM16A currents but had no effect on Best1 currents. Tannic acid, NPPB and FFA had variable intermediate effects. Potentiation of channel activity by some of these modulators and the effects on TMEM16A deactivation kinetics were also described. Characterization of Cl?/sup> channel modulators for their effects on TMEM16A and Best1 will facilitate future studies of native CaCCs.