Lambert-Eaton myasthenic syndrome (LEMS) is an autoimmune synaptic disease characterized by a widespread deficiency in depolarization-induced neurotransmitter release from nerve terminals (see ref. 1 for a recent review). Over the last decade a lot of evidence has accumulated, suggesting that voltage-operated calcium channels (VOCC) are the molecular targets of this autoimmune syndrome.*A.s~ neuronal VOCCs form a large family of heterogeneous proteins,4-’ the question is posed, On which VOCC subtypes do LEMS autoantibodies act? Identification and characterization of neuronal VOCCs is not an easy task. Old criteria’O based on kinetic differences among channel subtypes have been proved mostly inappropriate.’.” Presently, many laboratories are convinced that a more pharmacological approach based on the different sensitivity of the channels to drugs and toxins leads to more reliable results (TABLEI). Following these criteria, we have recently demonstrated that neurosecretory cells, previously believed to possess a single VOCC, may indeed express multiple VOCC s~btypesl*-a’n~d that LEMS autoantibodies recognize a VOCC subtype specifically labeled by w-conotoxin (w-Ctx). We will describe here our present knowledge of VOCC subtypes in neurosecretory cells, their pharmacological and functional relevance, and their role as autoantigens in LEMS.
Neuronal calcium channels as target for Lambert-Eaton myasthenic syndrome autoantibodies
CARBONE, Emilio;
1993-01-01
Abstract
Lambert-Eaton myasthenic syndrome (LEMS) is an autoimmune synaptic disease characterized by a widespread deficiency in depolarization-induced neurotransmitter release from nerve terminals (see ref. 1 for a recent review). Over the last decade a lot of evidence has accumulated, suggesting that voltage-operated calcium channels (VOCC) are the molecular targets of this autoimmune syndrome.*A.s~ neuronal VOCCs form a large family of heterogeneous proteins,4-’ the question is posed, On which VOCC subtypes do LEMS autoantibodies act? Identification and characterization of neuronal VOCCs is not an easy task. Old criteria’O based on kinetic differences among channel subtypes have been proved mostly inappropriate.’.” Presently, many laboratories are convinced that a more pharmacological approach based on the different sensitivity of the channels to drugs and toxins leads to more reliable results (TABLEI). Following these criteria, we have recently demonstrated that neurosecretory cells, previously believed to possess a single VOCC, may indeed express multiple VOCC s~btypesl*-a’n~d that LEMS autoantibodies recognize a VOCC subtype specifically labeled by w-conotoxin (w-Ctx). We will describe here our present knowledge of VOCC subtypes in neurosecretory cells, their pharmacological and functional relevance, and their role as autoantigens in LEMS.File | Dimensione | Formato | |
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Sher et al Ann NY Acad Sci (USA) 1993.pdf
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