Glial Neurobiology A Textbook Alexei Verkhratsky University of Manchester Arthur Butt University of Portsmouth Glial Neurobiology Glial Neurobiology A Textbook Alexei Verkhratsky University of Manchester Arthur Butt University of Portsmouth Copyright©2007 JohnWiley&SonsLtd,TheAtrium,SouthernGate,Chichester, WestSussexPO198SQ,England Telephone (cid:2)+44(cid:3)1243779777 Email(forordersandcustomerserviceenquiries):[email protected] VisitourHomePageonwww.wiley.com AllRightsReserved.Nopartofthispublicationmaybereproduced,storedinaretrievalsystemor transmittedinanyformorbyanymeans,electronic,mechanical,photocopying,recording,scanningor otherwise,exceptunderthetermsoftheCopyright,DesignsandPatentsAct1988orunderthetermsofa licenceissuedbytheCopyrightLicensingAgencyLtd,90TottenhamCourtRoad,LondonW1T4LP,UK, withoutthepermissioninwritingofthePublisher.RequeststothePublishershouldbeaddressedtothe PermissionsDepartment,JohnWiley&SonsLtd,TheAtrium,SouthernGate,Chichester,WestSussex PO198SQ,England,[email protected],orfaxedto(+44)1243770620. Designationsusedbycompaniestodistinguishtheirproductsareoftenclaimedastrademarks.Allbrand namesandproductnamesusedinthisbookaretradenames,servicemarks,trademarksorregistered trademarksoftheirrespectiveowners.ThePublisherisnotassociatedwithanyproductorvendor mentionedinthisbook. Thispublicationisdesignedtoprovideaccurateandauthoritativeinformationinregardtothesubject mattercovered.ItissoldontheunderstandingthatthePublisherisnotengagedinrenderingprofessional services.Ifprofessionaladviceorotherexpertassistanceisrequired,theservicesofacompetent professionalshouldbesought. OtherWileyEditorialOffices JohnWiley&SonsInc.,111RiverStreet,Hoboken,NJ07030,USA Jossey-Bass,989MarketStreet,SanFrancisco,CA94103-1741,USA Wiley-VCHVerlagGmbH,Boschstr.12,D-69469Weinheim,Germany JohnWiley&SonsAustraliaLtd,33ParkRoad,Milton,Queensland4064,Australia JohnWiley&Sons(Asia)PteLtd,2ClementiLoop#02-01,JinXingDistripark,Singapore129809 JohnWiley&SonsCanadaLtd,6045FreemontBlvd,Mississauga,Ontario,L5R4J3 Wileyalsopublishesitsbooksinavarietyofelectronicformats.Somecontentthatappearsinprintmay notbeavailableinelectronicbooks. AnniversaryLogoDesign:RichardJ.Pacifico LibraryofCongressCataloginginPublicationData Verkhratskii,A.N.(AlekseiNestorovich) Glialneurobiology:atextbook/AlexeiVerkhratsky,ArthurButt. p. ; cm. Includesbibliographicalreferencesandindex. ISBN978-0-470-01564-3(cloth:alk.paper) 1. Neuroglia. I. Butt,Arthur. II.Title. [DNLM:1.Neuroglia.WL102V519g2007] QP363.2.V472007 611(cid:2).0188—dc22 2007015819 BritishLibraryCataloguinginPublicationData AcataloguerecordforthisbookisavailablefromtheBritishLibrary ISBN978-0-470-01564-3(HB) ISBN978-0-470-51740-6(PB) Typesetin10.5/12.5ptTimesbyIntegraSoftwareServicesPvt.Ltd,Pondicherry,India PrintedandboundinGreatBritainbyAntonyRoweLtd,Chippenham,Wiltshire Thisbookisprintedonacid-freepaperresponsiblymanufacturedfromsustainableforestryinwhich atleasttwotreesareplantedforeachoneusedforpaperproduction. Dedicated to our Families Contents Preface xi List of abbreviations xiii PART I Physiology of Glia 1 1 Introduction to Glia 3 1.1 Foundersofglialresearch:fromGabrielValentintoKarl-LudwigSchleich 3 1.2 Beginningofthemodernera 11 1.3 Changingconcepts:Gliaexpressmoleculesofexcitation 11 1.4 Gliaandneuronesindialogue 12 2 General Overview of Signalling in the Nervous System 13 2.1 Intercellularsignalling:Wiringandvolumemodesoftransmission 13 2.2 Intracellularsignalling 17 3 Morphology of Glial Cells 21 3.1 Astrocytes 21 3.2 Oligodendrocytes 24 3.3 NG2expressingglia 26 3.4 Schwanncells 27 3.5 Microglia 28 4 Glial Development 29 4.1 Phylogenyofgliaandevolutionaryspecificityofglialcellsinhumanbrain 29 4.2 Macroglialcells 32 4.3 Astroglialcellsarebrainstemcells 35 4.4 Schwanncelllineage 36 4.5 Microglialcelllineage 37 5 General Physiology of Glial Cells 39 5.1 Membranepotentialandiondistribution 39 5.2 Ionchannels 39 5.3 Receptorstoneurotransmittersandneuromodulators 42 5.4 Glialsyncytium–gapjunctions 58