Homozygous mutations in VAMP1 cause a presynaptic congenital myasthenic syndrome
Salpietro V, Lin W, Delle Vedove A, Storbeck M, Liu Y, Efthymiou S, Manole A, Wiethoff S, Ye Q, Saggar A, McElreavey K, Krishnakumar SS, Group S, Pitt M, Bello OD, Rothman JE, Basel‐Vanagaite L, Hubshman MW, Aharoni S, Manzur AY, Wirth B, Houlden H. Homozygous mutations in VAMP1 cause a presynaptic congenital myasthenic syndrome. Annals Of Neurology 2017, 81: 597-603. PMID: 28253535, PMCID: PMC5413866, DOI: 10.1002/ana.24905.Peer-Reviewed Original ResearchConceptsPresynaptic congenital myasthenic syndromeCongenital myasthenic syndromePresynaptic impairmentMyasthenic syndromeLow compound muscle action potentialsNeuromuscular junctionCompound muscle action potentialPresynaptic neuromuscular junctionHomozygous mutationMuscle action potentialsAnn NeurolNMJ transmissionElectrodiagnostic examinationNeurophysiological featuresAction potentialsLew/Homozygous variantMRNA levelsSyndromeWhole exomeImpairmentVAMP1Kuwaiti familyNonsense mutationMutationsKv1.1 channelopathy abolishes presynaptic spike width modulation by subthreshold somatic depolarization
Vivekananda U, Novak P, Bello OD, Korchev YE, Krishnakumar SS, Volynski KE, Kullmann DM. Kv1.1 channelopathy abolishes presynaptic spike width modulation by subthreshold somatic depolarization. Proceedings Of The National Academy Of Sciences Of The United States Of America 2017, 114: 2395-2400. PMID: 28193892, PMCID: PMC5338558, DOI: 10.1073/pnas.1608763114.Peer-Reviewed Original ResearchConceptsSomatic depolarizationPotassium channelsAction potentialsPresynaptic potassium channelsPrimary hippocampal culturesSubthreshold membrane potential fluctuationsHeterozygous mouse modelEpisodic ataxia type 1Distinct potassium channelsSubthreshold modulationAxon transectionSmall boutonsCalcium influxHippocampal culturesMouse modelSynaptic boutonsKv1.1 subunitsMembrane potential fluctuationsNeurotransmitter releaseIntact axonsType 1Genetic deletionAtaxia type 1Further prolongationPresynaptic spikes