大会2015集葡萄糖对神经动力学的影响

*（华东理工大学认知神经动力学，动（其是萄的模拟神元不葡糖量件的况并一究与经元相的子道特性从表了同葡糖量神元式生的质。 MCH神经元[1-4]。这些神经元所摄取的葡萄糖的含量会影响其模式；反之，由此神经元的激活ATP介导的离子通道机制(KATP通道的开闭)也会反过来调节细胞内的葡萄糖稳态。目前已有一些研究成果解释了这些葡萄糖感受神经元受葡萄糖激活的过程，其具体机制与胰岛β细KATP通道关闭，促进细胞膜去极化。如前所述，葡萄糖感受神经元对血糖的调控机制与胰岛β细胞类似。本文参考了芝加哥大学及大学的一些学者胰岛β细胞模型[8-12]，此模型是由类H-H细胞膜模型扩展而来的，图1所示，该模型主要包括了细胞膜、线粒体和内质网三个部分。细胞膜上有Na+、K+、Ca2+、Cl-Ca2+稳态的调节，还通过与线粒1葡萄糖感受神经元模型示意图。它包括三部分。(1)膜上的离子流:INa,钠电流;IKI,内向整流钾电流;IKATP,ATP敏感钾电流;IKr,快速延迟整流钾电流;IKs,慢速延迟整流钾电流;Ito,瞬时内向电流;ICaL,L型钙电流;ICaTT型钙电流;IPMCA,细胞膜钙泵电流;ICab,背景钙电流;INaK,钠钾泵电流;INaCa,Na+/Ca2+离子交换泵电流;INKb,非选择性阳离子(Na+K+)电流Il(Ca),钙激活介导的阳离子电流;IClb,背景氯电流;(2)线粒体;(3)内质网内Ca2+动力学:IERCA,Ca2+摄取有关的内质网钙泵电流;Irel,Ca2+释放电流。2细胞膜的等效电路图[8]。Vm为膜电位(mVCm为膜电容(Cm=1pF,同下Ex为平衡电位IY的电流Im

dVm

ImINaIKIIKrIKsItoICaLICaTINaKINaCaIPMCAIlINKbIKATPICabIClbIl

此，胞内外离子浓度与膜电位的关系用Goldman-Hodgkin-Katz方程描述为：[X]z

expzXFVm CFX

zFV m 其中，F为法拉第常数,96.4867Cmmol-1;R为气体常数,8.3143CmVK-1mmol-1;T为绝对温度,单位为K。 dKInetK 其中Vi为允许离子扩散的细胞体积；InetX表示含XInetKIKIIKrIKATPItoKIKsKINaKICaLKIl(Ca)KINKbK

RT z GKInetK2INaK/VmEK

结在不同的葡萄糖含量下，葡萄糖感受神经元的模式会发生变化，其率随葡萄糖含量而变化的情况如图3所示，此结果与胰岛β细胞的仿真结果[11]类似。可以看出，当葡萄糖含量较低量后，神经元会开始。而且随着葡萄糖含量的增加，神经元的模式会变为簇，率12mM时的变化情况。Claret,M.,Smith,M.A.,Batterham,R.L.,etal.AMPKisessentialforenergyhomeostasisregulationandglucosesensingbyPOMCandAgRPneurons.J.Clin.Invest.,2007,117:2325~2336Ibrahim,N,Bosch,M.A,Smart,J.L.etal.HypothalamicproopiomelanocortinneuronsareglucoseresponsiveandexpressK(ATP)channels.Parton,L.E.,Ye,C.P,Coppari,R.,etal.GlucosesensingbyPOMCneuronsregulatesglucosehomeostasisandisimpairedinobesity.Nature,2007,Kong,D,Vong,L.,Parton,LE.,etal.GlucoseStimulationofHypothalamicMCHNeuronsInvolvesKATPChannels,IsModulatedbyUCP2,andRegulatesPeripheralGlucoseHomeostasis.CellMetabolism,2010,12:545~552Balfour,R.H.,Hansen,A.M.,andTrapp,S.Neuronalresponsestotransienthypoglycaemiainthedorsalvagalcomplexoftheratbrainstem.J.Physiol.,2006,570:469~484Burdakov,D.,Gerasimenko,O.,andVerkhratsky,A.Physiologicalchangesinglucosedifferentiallymodulatetheexcitabilityofhypothalamicmelanin-concentratinghormoneandorexinneuronsinsitu.J.Neurosci.,2005,25:2429~2433FridlyandLE,TamarinaN,PhilipsonLH.Burstingandcalciumoscillationsinpancreaticβ-cells:specificpacemakersforspecificmechanisms.AmJPhysiolEndocrinolMetab,2010,299:517~532Byrne,J.H.,Roberts,JL.Frommoleculestonetworks:Anintroductiontocellularandmolecularneuronscience,2ndedn.Beijing:SciencePress,Cha,C.Y,Powell,T.,Noma,A.yzingelectricalactivitiesofpancreaticβcellsusingmathematicalmodels.ProgressinBiophysicsCha,C.Y,Nakamura,Y,Himeno,Y.,etal.IonicmechanismsandCa2+dynamicsunderlyingtheglucoseresponseofpancreaticsimulationstudy.J.Gen.Physiol.,2011,138(1):21~37

cells:Takeuchi,A,Tatsumi,S,Sarai,N.,etal.IonicMechanismsofCardiacCellSwellingInducedbyBlockingNa+/K+PumpAsRevealedbyExperimentsandSimulation.J.Gen.Physiol.,2006,128(5):495~507Rueda,C.B.,Llorente-Folch,I.,Amigo,I.,etal.Ca2+regulationofmitochondrialfunctioninneurons.BiochimicaetPatergnani,S.,Suski,J.M.,Agnoletto,C.,etal.CalciumsignalingaroundMitochondriaAssociatedMembranes(MAMs).CellCommunTHEINFLUNCEOFGLUCOSEONNEURONAL WANG(1TheInstitutionforCognitiveNeurodynamics,EastUniversityofScienceandTechnology,No.130MeilongRoad,Shanghai200237,)Anadequateenergysupplyiscrucialtomaintainnormalnervefunctionsofthebrain.Thereareglucose-excitedneuronsinthebrainthatcansensebloodglu