大會(huì)2015集葡萄糖對(duì)神經(jīng)動(dòng)力學(xué)的影響

*（華東理工大學(xué)認(rèn)知神經(jīng)動(dòng)力學(xué)，動(dòng)（其是萄的模擬神元不葡糖量件的況并一究與經(jīng)元相的子道特性從表了同葡糖量神元式生的質(zhì)。 MCH神經(jīng)元[1-4]。這些神經(jīng)元所攝取的葡萄糖的含量會(huì)影響其模式；反之，由此神經(jīng)元的激活A(yù)TP介導(dǎo)的離子通道機(jī)制(KATP通道的開閉)也會(huì)反過來調(diào)節(jié)細(xì)胞內(nèi)的葡萄糖穩(wěn)態(tài)。目前已有一些研究成果解釋了這些葡萄糖感受神經(jīng)元受葡萄糖激活的過程，其具體機(jī)制與胰島β細(xì)KATP通道關(guān)閉，促進(jìn)細(xì)胞膜去極化。如前所述，葡萄糖感受神經(jīng)元對(duì)血糖的調(diào)控機(jī)制與胰島β細(xì)胞類似。本文參考了芝加哥大學(xué)及大學(xué)的一些學(xué)者胰島β細(xì)胞模型[8-12]，此模型是由類H-H細(xì)胞膜模型擴(kuò)展而來的，圖1所示，該模型主要包括了細(xì)胞膜、線粒體和內(nèi)質(zhì)網(wǎng)三個(gè)部分。細(xì)胞膜上有Na+、K+、Ca2+、Cl-Ca2+穩(wěn)態(tài)的調(diào)節(jié)，還通過與線粒1葡萄糖感受神經(jīng)元模型示意圖。它包括三部分。(1)膜上的離子流:INa,鈉電流;IKI,內(nèi)向整流鉀電流;IKATP,ATP敏感鉀電流;IKr,快速延遲整流鉀電流;IKs,慢速延遲整流鉀電流;Ito,瞬時(shí)內(nèi)向電流;ICaL,L型鈣電流;ICaTT型鈣電流;IPMCA,細(xì)胞膜鈣泵電流;ICab,背景鈣電流;INaK,鈉鉀泵電流;INaCa,Na+/Ca2+離子交換泵電流;INKb,非選擇性陽離子(Na+K+)電流Il(Ca),鈣激活介導(dǎo)的陽離子電流;IClb,背景氯電流;(2)線粒體;(3)內(nèi)質(zhì)網(wǎng)內(nèi)Ca2+動(dòng)力學(xué):IERCA,Ca2+攝取有關(guān)的內(nèi)質(zhì)網(wǎng)鈣泵電流;Irel,Ca2+釋放電流。2細(xì)胞膜的等效電路圖[8]。Vm為膜電位(mVCm為膜電容(Cm=1pF,同下Ex為平衡電位IY的電流Im

dVm

ImINaIKIIKrIKsItoICaLICaTINaKINaCaIPMCAIlINKbIKATPICabIClbIl

此，胞內(nèi)外離子濃度與膜電位的關(guān)系用Goldman-Hodgkin-Katz方程描述為：[X]z

expzXFVm CFX

zFV m 其中，F(xiàn)為法拉第常數(shù),96.4867Cmmol-1;R為氣體常數(shù),8.3143CmVK-1mmol-1;T為絕對(duì)溫度,單位為K。 dKInetK 其中Vi為允許離子擴(kuò)散的細(xì)胞體積；InetX表示含XInetKIKIIKrIKATPItoKIKsKINaKICaLKIl(Ca)KINKbK

RT z GKInetK2INaK/VmEK

結(jié)在不同的葡萄糖含量下，葡萄糖感受神經(jīng)元的模式會(huì)發(fā)生變化，其率隨葡萄糖含量而變化的情況如圖3所示，此結(jié)果與胰島β細(xì)胞的仿真結(jié)果[11]類似?？梢钥闯?，當(dāng)葡萄糖含量較低量后，神經(jīng)元會(huì)開始。而且隨著葡萄糖含量的增加，神經(jīng)元的模式會(huì)變?yōu)榇?，?2mM時(shí)的變化情況。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