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1、Metaboliccommunicationbetweenastrocytesandneuronsviabicarbonate-responsivesolubleadenylylcyclaseHyunB.Choi1,GrantR.J.Gordon1,NingZhou1,3,ChaoTai1,JenniferMartinez4,TeresaA.Milner5,JaeK.Ryu2,JamesG.McLarnon2,MartinTresguerres4LonnyR.Levin4,JochenBuck4,BrianA.MacVicar1,*
2、1BrainResearchCentre,DepartmentofPsychiatry,UniversityofBritishColumbia,Vancouver,BCV6T2B5,Canada2DepartmentofAnesthesiology,Pharmacology,andTherapeutics,DepartmentofMedicine,UniversityofBritishColumbia,Vancouver,BCV6T2B5,Canada3TranslationalMedicineResearchCenter,Chin
3、aMedicalUniversityHospital,Taichung40402,Taiwan4DepartmentofPharmacology,WeillCornellMedicalCollege,NewYork,NY10021,USA5DepartmentofNeurologyandNeuroscience,WeillCornellMedicalCollege,NewYork,NY10065,USA*CorrespondingAuthor:BrianA.MacVicar,PhDBrainResearchCentre,Depart
4、mentofPsychiatry,UniversityofBritishColumbia,2211WesbrookMall,Vancouver,BC,V6T2B5,CanadaTelephone:(604)822-7797Fax:(604)822-7299E-mail:bmacvicar@brain.ubc.ca28Astrocytesareproposedtoparticipateinbrainenergymetabolismbysupplyingsubstratestoneuronsfromtheirglycogenstores
5、andfromglycolysis.However,themoleculesinvolvedinmetabolicsensingandthemolecularpathwaysresponsibleformetaboliccouplingbetweendifferentcelltypesinthebrainarenotfullyunderstood.Hereweshowthatarecentlyclonedbicarbonate(HCO3-)sensor,solubleadenylylcyclase(sAC),ishighlyexpr
6、essedinastrocytesandbecomesactivatedinresponsetoHCO3-entryviatheelectrogenicNaHCO3cotransporter(NBC).ActivatedsACincreasestheintracellularcAMPlevelcausingglycogenbreakdown,enhancedglycolysisandthereleaseoflactateintotheextracellularspace,whichissubsequentlytakenupbyneu
7、ronsforuseasanenergysubstrate.Thisprocessisrecruitedoverabroadphysiologicalrangeof[K+]extandalsoduringaglycemicepisodes,helpingtomaintainsynapticfunction.Thesedatarevealanovelmolecularpathwayinastrocytesthatisresponsibleforbrainmetaboliccoupling.Astrocytesalonemakeands
8、toreglycogeninthemammalianadultbrain1.Byrecruitingthisenergystore,astrocytescandeliverlactate(andpossiblypyruvate)ton
