《离子通道生物学》课程教学课件（英文讲稿）Ion channel diseases（1/2）

lon channel(diseasesJie Zhang,Binghua Lu,Shaoui Liu,Meng Zhang,Li Feng.Junwei Yao,Cheng LongSchool of Life Sciences, South China Normal UniversityApril 10, 20121933華南轩范大学UNIVERSITYSOUTH CHINA NORSMAL

Ion channel diseases Jie Zhang, Binghua Lu, Shaoui Liu, Meng Zhang, Li Feng, Junwei Yao, Cheng Long School of Life Sciences, South China Normal University April 10, 2012

ReferencesRajakulendranS,KaskiD,HannaMG.(2012)NeuronalP/Q-typecalciumchannel dysfunction ininheriteddisorders of the CNS.Nat Rev Neurol.8(2):86-96.CerroneM,NapolitanoC,PrioriSG.(2012)GeneticsofChannelion-channeldisorders.CurrOpinCardiol.2012MarDiseases23.[Epubaheadofprint]KleopaKA.(2011)Autoimmunechannelopathiesofthenervoussystem.CurrNeuropharmacol.9(3):458-tlSny Bnlea467.CietaapuValverde MA,Cantero-Recasens G, Garcia-Elias A, JungC,Carreras-SuredaA,VicenteR.(2011)lonIonChannelschannelsinasthma.JBiolChem.286(38):32877-andDisease32882.Frances M. AshcroftTesterDJ,Ackerman MJ.(2011)Genetictestingforpotentially lethal,highly treatable inheritedycardiomyopathies/channelopathiesinclinical办practice.Circulation.123(9):1021-1037.KullmannDM.(2010)Neurologicalchannelopathies.AnnuRevNeurosci.33:151-172

References Rajakulendran S, Kaski D, Hanna MG. (2012) Neuronal P/Q-type calcium channel dysfunction in inherited disorders of the CNS. Nat Rev Neurol. 8(2): 86-96. Cerrone M, Napolitano C, Priori SG. (2012) Genetics of ion-channel disorders. Curr Opin Cardiol. 2012 Mar 23. [Epub ahead of print] Kleopa KA. (2011) Autoimmune channelopathies of the nervous system. Curr Neuropharmacol. 9(3): 458- 467. Valverde MA, Cantero-Recasens G, Garcia-Elias A, Jung C, Carreras-Sureda A, Vicente R. (2011) Ion channels in asthma. J Biol Chem. 286(38): 32877- 32882. Tester DJ, Ackerman MJ. (2011) Genetic testing for potentially lethal, highly treatable inherited cardiomyopathies/channelopathies in clinical practice. Circulation. 123(9): 1021-1037. Kullmann DM. (2010) Neurological channelopathies. Annu Rev Neurosci. 33: 151–172

ReferencesDib-HajSD,CumminsTR,BlackJA,WaxmanSG.(2010).Sodiumchannels in normal and pathologicalpain.AnnuRevNeurosci.33:325-347.CannonSC.(2010)Voltage-sensormutationsinchannelopathiesofskeletalmuscle.JPhysiol.588(11):1887-1895.BetzenhauserMJ,MarksAR.(2010)Ryanodinereceptorchannelopathies.PflugersArch-EurJPhysiol.460(2):467-480RaoufR,QuickK,WoodJN.(2010)Painasachannelopathy.JClinInvest.120(11):3745-3752GalanopoulouAS.(2010)MutationsaffectingGABAergicsignalinginseizuresandepilepsy.PflugersArch-EurJPhysiol.460(2):505-523.LoryP,MezghraniA.(2010)Calciumchannelopathiesininheritedneurological disorders:relevance to drug screening for acquiredchanneldisorders.IDrugs.13(7):467-471RyanDP,PtacekLJ.(2010)EpisodicneurologicalchannelopathiesNeuron.68(2):282-292

References Dib-Hajj SD, Cummins TR, Black JA, Waxman SG. (2010). Sodium channels in normal and pathological pain. Annu Rev Neurosci. 33: 325–347. Cannon SC. (2010) Voltage-sensor mutations in channelopathies of skeletal muscle. J Physiol. 588(11): 1887–1895. Betzenhauser MJ, Marks AR. (2010) Ryanodine receptor channelopathies. Pflugers Arch - Eur J Physiol. 460(2): 467–480. Raouf R, Quick K, Wood JN. (2010) Pain as a channelopathy. J Clin Invest. 120(11): 3745–3752. Galanopoulou AS. (2010) Mutations affecting GABAergic signaling in seizures and epilepsy. Pflugers Arch - Eur J Physiol. 460(2): 505– 523. Lory P, Mezghrani A. (2010) Calcium channelopathies in inherited neurological disorders: relevance to drug screening for acquired channel disorders. IDrugs. 13(7): 467-471. Ryan DP, Ptácek LJ. (2010) Episodic neurological channelopathies. Neuron. 68(2): 282-292

ReferencesRolimAL,LindseySC,KuniiIS,FujikawaAM,SoaresFA,ChiamoleraMlMacielRM,SilvaMR.(2010)lonchannelopathiesinendocrinology:recent genetic findingsand pathophysiologicalinsights.ArgBrasEndocrinolMetabol.54(8):673-681.CreggR,MominA,RugieroF,WoodJN,ZhaoJ.(2010)Painchannelopathies.JPhysiol.588(11):1897-1904.KullmannDM,WaxmanSG.(2010)Neurologicalchannelopathies:newinsightsintodiseasemechanismsand ionchannelfunction.JPhysiol.588(11):1823-1827RajaRayanDL,HannaMG.(2010)Skeletalmusclechannelopathies:nondystrophicmyotoniasandperiodicparalysis.CurrOpinNeurol.23(5):466-476Catterall WA,Dib-HajS,MeislerMH,PietrobonD.(2008)Inheritedneuronalionchannelopathies:newwindowsoncomplexneurologicaldiseases.JNeurosci.28(46):11768-11777PietrobonD.(2oo2)Calciumchannelsandchannelopathiesofthecentralnervoussystem.MolNeurobiol.25(1):31-50

References Rolim AL, Lindsey SC, Kunii IS, Fujikawa AM, Soares FA, Chiamolera MI, Maciel RM, Silva MR. (2010) Ion channelopathies in endocrinology: recent genetic findings and pathophysiological insights. Arq Bras Endocrinol Metabol. 54(8): 673-681. Cregg R, Momin A, Rugiero F, Wood JN, Zhao J. (2010) Pain channelopathies. J Physiol. 588(11): 1897-1904. Kullmann DM, Waxman SG. (2010) Neurological channelopathies: new insights into disease mechanisms and ion channel function. J Physiol. 588(11): 1823-1827. Raja Rayan DL, Hanna MG. (2010) Skeletal muscle channelopathies: nondystrophic myotonias and periodic paralysis. Curr Opin Neurol. 23(5): 466-476. Catterall WA, Dib-Hajj S, Meisler MH, Pietrobon D. (2008) Inherited neuronal ion channelopathies: new windows on complex neurological diseases. J Neurosci. 28(46): 11768-11777. Pietrobon D. (2002) Calcium channels and channelopathies of the central nervous system. Mol Neurobiol. 25(1): 31-50

lonchanneldiseaselonchanneldisorderlonchannelopathyChannelopathiesarediseasescausedbydisturbedfunctionofionchannel subunits ortheproteinsthatregulatethem.Geneticdisordersofionchannelsandtheirmodifiersare known as channelopathies.Channelopathiesareassociatedwithawidevarietyofsymptoms

Ion channel disease Ion channel disorder Ion channelopathy  Channelopathies are diseases caused by disturbed function of ion channel subunits or the proteins that regulate them.  Genetic disorders of ion channels and their modifiers are known as channelopathies.  Channelopathies are associated with a wide variety of symptoms

Mutations in many classes of ion channelsare associatedwithhuman diseaseIIDutnNavFHM3PAM?PMCGEFS+PEPDHyperKPpHypoKPpErythermelgiaOutCIPOut10InKvKirBFNCEAIATSKJ-LNSCA13TPPLongQTAtrialFibrillationIXT儿CavCAEHypoKPpEA5LongQTSCA6/EA2/FHM1

Mutations in many classes of ion channels are associated with human disease

Genotype-phenotype correlationsin Long QT syndromeKCNQ1(LQT1)KCNH2(LQT2)BetaBetaBlockersBiockersn10030%8035%40402080Swimming60EanoExertionOE40PostpartumPeriodAuditoryTriggersSCN5A(LQT3)1008品导品BetaMexletineBlockers10%SeDCeSleep/Rest

Genotype-phenotype correlations in Long QT syndrome

lon channelsassociated withpainsyndromesTRANSDUCTIONMODULATIONMIGRAINEHeatColdDamagemediatorsATP1A2InhibitorycircuitsTRPV1TRPM8P2X3P2X4P2X7Cav2.1,GLYRC-3.NKKC1TRPV2TRPA15-HT3TRPV1TRPA1MicroglialActivationNav1.1TRPV3ASICSATPviaP2X4.P2X7TRPV4MechanosensationP2X3TRPV4,TRPC/V/P?Alteredpainthresholds0000TRPV1,Nav1.5,Nav1.7,Nav1.8,Nav1.9KCNQ.K2PKVIHCNTRANSMISSIONNav1.7.Nav1.8,Nav1.1Nav1.2,Nav1.6, (Nav1.3)Threshold-Nav1.9VISCERALPAINNav1.5,Nav1.8TRANSMITTERRELEASENav1.9Cav2.1,Cav2.2.Cav3.1,Cav3.2.a2d1

Ion channels associated with pain syndromes

Your turn

Your turn

水Calcium and Alzheimer's DiseaseJieZhang

Jie Zhang