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dc.contributor.authorCastilho, Aurea
dc.contributor.authorMadsen, Eirik
dc.contributor.authorAmbrósio, António F.
dc.contributor.authorVeruki, Margaret Lin
dc.contributor.authorHartveit, Espen
dc.date.accessioned2018-01-05T12:39:11Z
dc.date.available2018-01-05T12:39:11Z
dc.date.issued2015-09
dc.identifier.citationCastilho A, Madsen, Ambrósio AF, Veruki ML, Hartveit E. Diabetic hyperglycemia reduces Ca2+ permeability of extrasynaptic AMPA receptors in AII amacrine cells. Journal of Neurophysiology. 2015;114(3):1545-1553eng
dc.identifier.urihttp://hdl.handle.net/1956/17151
dc.description.abstractThere is increasing evidence that diabetic retinopathy is a primary neuropathological disorder that precedes the microvascular pathology associated with later stages of the disease. Recently, we found evidence for altered functional properties of synaptic α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors in A17, but not AII, amacrine cells in the mammalian retina, and the observed changes were consistent with an upregulation of the GluA2 subunit, a key determinant of functional properties of AMPA receptors, including Ca2+ permeability and current-voltage (I-V) rectification properties. Here, we have investigated functional changes of extrasynaptic AMPA receptors in AII amacrine cells evoked by diabetes. With patch-clamp recording of nucleated patches from retinal slices, we measured Ca2+ permeability and I–V rectification in rats with ∼3 wk of streptozotocin-induced diabetes and age-matched, noninjected controls. Under bi-ionic conditions (extracellular Ca2+ concentration = 30 mM, intracellular Cs+ concentration = 171 mM), the reversal potential (Erev) of AMPA-evoked currents indicated a significant reduction of Ca2+ permeability in diabetic animals [Erev = −17.7 mV, relative permeability of Ca2+ compared with Cs+ (PCa/PCs) = 1.39] compared with normal animals (Erev = −7.7 mV, PCa/PCs = 2.35). Insulin treatment prevented the reduction of Ca2+ permeability. I–V rectification was examined by calculating a rectification index (RI) as the ratio of the AMPA-evoked conductance at +40 and −60 mV. The degree of inward rectification in patches from diabetic animals (RI = 0.48) was significantly reduced compared with that in normal animals (RI = 0.30). These results suggest that diabetes evokes a change in the functional properties of extrasynaptic AMPA receptors of AII amacrine cells. These changes could be representative for extrasynaptic AMPA receptors elsewhere in AII amacrine cells and suggest that synaptic and extrasynaptic AMPA receptors are differentially regulated.eng
dc.language.isoengeng
dc.publisherAmerican Physiological Societyeng
dc.subjectamacrine cellseng
dc.subjectdiabeteseng
dc.subjectretinaeng
dc.subjectcalcium-permeable AMPA receptorseng
dc.titleDiabetic hyperglycemia reduces Ca2+ permeability of extrasynaptic AMPA receptors in AII amacrine cellseng
dc.typeJournal articleeng
dc.date.updated2017-10-21T11:34:26Z
dc.rights.holderCopyright 2015 the American Physiological Societyeng
dc.type.versionacceptedVersioneng
bora.peerreviewedPeer reviewedeng
dc.type.documentJournal article
dc.identifier.cristinID1266157
dc.identifier.doi10.1152/jn.00295.2015eng
dc.source.issn0022-3077eng
dc.source.issn1522-1598eng
dc.relation.projectIDNorges forskningsråd: 189662
dc.relation.projectIDNorges forskningsråd: 182743
dc.relation.projectIDHelse Vest RHF: 911349
dc.relation.projectIDNorges forskningsråd: 213776
dc.relation.projectIDNorges forskningsråd: 178105
dc.relation.journalJournal of Neurophysiology


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