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Reference: Leys, Katherine S., (1991). Characterisation of voltage-gated calcium channels and detection of their autoantibodies. DPhil. University of Oxford.Citable link to this page:

 

Characterisation of voltage-gated calcium channels and detection of their autoantibodies

Abstract: The Lambert-Eaton myasthenic syndrome (LEMS) is an autoimmunedisorder of impaired neuromuscular transmission. It is associatedwith small cell lung carcinoma (SCLC) in 60% of patients. There isconsiderable evidence that the defect in LEMS is caused byautoantibodies to voltage-gated calcium channels (VGCCs) on thenerve terminal.Two VGCC subtypes were demonstrated in cultured neuronal celllines by the technique of K+-induced 45Ca2+ influx: one subtype wasinhibited by dihydropyridines (DHPs), the other by ω-conotoxin(ωCgTx). These may correspond to L and N channels previouslydescribed for neuronal tissue. The presence of these VGCC subtypeswas confirmed by radioligand binding studies using [3 Hj-PN200-11 0 and125 I-d)ωCgTx respectively.Pooled LEMS IgG inhibited K+-induced Ca2+ flux by 40% in SKNSH(human neuroblastoma) cells, while control IgG had no effect. Thesame LEMS pool reduced the density of 125I-ωCgTx binding sites inSKNSH and MAR5 (human SCLC) cells by 57% and 43% respectively.These results provide further evidence that LEMS antibodies causea loss of functional VGCCs.78 LEMS and 88 control sera were tested for anti-VGCC antibodiesby the precipitation of 125I-ωCgTx-labelled VGCCs extracted fromSKNSH cells. 42% of LEMS sera had significant levels of antibody(30-1466pM) compared to the healthy controls (



Author: Leys, Katherine S. - institutionUniversity of Oxford facultyMedical Sciences Division - - - - Contributors Lang, Bethan More by t

Source: https://ora.ox.ac.uk/objects/uuid:f8a39d64-6491-45ea-91a3-71f3f969fd07



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