Carbenoxolone Blocks the Light-Evoked Rise in Intracellular Calcium in Isolated Melanopsin Ganglion Cell Photoreceptors 英文参考文献.docVIP

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Carbenoxolone Blocks the Light-Evoked Rise in Intracellular Calcium in Isolated Melanopsin Ganglion Cell Photoreceptors 英文参考文献.doc

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Carbenoxolone Blocks the Light-Evoked Rise in Intracellular Calcium in Isolated Melanopsin Ganglion Cell Photoreceptors 英文参考文献

CarbenoxoloneBlockstheLight-EvokedRisein IntracellularCalciuminIsolatedMelanopsinGanglion CellPhotoreceptors JayneR.Bramley,ErinM.Wiles,PatriciaJ.Sollars,GaryE.Pickard* SchoolofVeterinaryMedicineandBiomedicalSciences,UniversityofNebraska,Lincoln,Nebraska,UnitedStatesofAmerica Abstract Background: Retinal ganglion cells expressing the photopigment melanopsin are intrinsically photosensitive (ipRGCs). Theseganglioncellphotoreceptorssendaxonstoseveralcentraltargetsinvolvedinavarietyoffunctions.Withintheretina ipRGCsprovideexcitatorydrivetodopaminergicamacrinecellsviaglutamatergicsignalsandipRGCsarecoupledtowide- fieldGABAergicamacrinecellsviagapjunctions.However,theextenttowhichipRGCsarecoupledtootherretinalneurons in theganglion cell layervia gapjunctions is unclear. Carbenoxolone, awidely employed gapjunction inhibitor, greatly reduces the number of retinal neurons exhibiting non-rod, non-cone mediated light-evoked Ca2+ signals suggesting extensiveintercellularcouplingbetweenipRGCsandnon-ipRGCsintheganglioncelllayer.However,carbenoxolonemay 2+ directlyinhibitlight-evokedCa signalsinipRGCsindependentofgapjunctionblockade. Methodology/PrincipalFindings:Totestthepossibilitythatcarbenoxolonedirectlyinhibitslight-evokedCa2+responsesin ipRGCs, the light-evoked rise in intracellular Ca2+ ([Ca ]) was examined using fura-2 imaging in isolated rat ipRGCs 2+ i maintained in short-term culture in the absence and presence of carbenoxolone. Carbenoxolone at 50 and 100 mM 2+ concentrations completely abolished the light-evoked rise in [Ca ]i in isolated ipRGCs. Recovery from carbenoxolone inhibitionwasvariable. Conclusions/Significance: We demonstrate that the light-evoked rise in [Ca2+]i in isolated mammalian ganglion cell 2+ photoreceptorsisinhibitedbycarbenoxolone.Sincethelight-evokedincreasein[Ca ]iinisolatedipRGCsisalmostentirely due to Ca entry via L-type voltage-gated calcium channels and carbenoxolone does not inhibit light-evoked action 2+ 2+ potentialfiringinipRG