Effect of Lambert-Eaton myasthenic syndrome antibodies on autonomic neurons in the mouse

被引:73
作者
Waterman, SA [1 ]
Lang, B [1 ]
NewsomDavis, J [1 ]
机构
[1] UNIV OXFORD, JOHN RADCLIFFE HOSP, INST MOL MED, DEPT PHARMACOL, OXFORD OX3 9DU, ENGLAND
关键词
D O I
10.1002/ana.410420204
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
Somatic muscle weakness and autonomic symptoms characterize the autoimmune Lambert-Eaton myasthenic syndrome (LEMS). The former results from IgG autoantibody-mediated down-regulation of P/Q-type voltage-gated calcium channels at motor nerve terminals and consequent reduction in acetylcholine release; the basis for the autonomic symptoms is unknown. Using omega-conocoxins GVIA and MVIIC and omega-agatoxin IVA that block N-, Q-, and P-type channels, we investigated ex vivo the calcium channels subserving transmitter release from postganglionic parasympathetic neurons in the bladder and from postganglionic sympathetic neurons in the vas deferens of mice injected with IgG from LEMS patients or from controls. Calcium influx through N-, P-, and Q-type channels subserved transmitter release from parasympathetic and sympathetic neurons in control mice. In test mice, the component of transmitter release subserved by P-type channels was abolished by four of four LEMS IgG preparations, that subserved by Q-type channels was significantly reduced by three, and that subserved by N-type channels by one. Thus, LEMS IgG impairs transmitter release from parasympathetic and sympathetic neurons through down-regulation of one or more subtypes of voltage-gated calcium channels. The results suggest chat antibody-mediated interference with specific ion channel function may also underlie autonomic dysfunction occurring in other autoimmune diseases.
引用
收藏
页码:147 / 156
页数:10
相关论文
共 50 条
[41]   CONGENITAL LAMBERT-EATON MYASTHENIC SYNDROME [J].
BADY, B ;
CHAUPLANNAZ, G ;
CARRIER, H .
ELECTROENCEPHALOGRAPHY AND CLINICAL NEUROPHYSIOLOGY, 1985, 61 (03) :S85-S85
[42]   CONGENITAL LAMBERT-EATON MYASTHENIC SYNDROME [J].
BADY, B ;
CHAUPLANNAZ, G ;
CARRIER, H .
JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY, 1987, 50 (04) :476-478
[43]   Retropulsion in Lambert-Eaton myasthenic syndrome [J].
Sonoo, M. ;
Hatanaka, Y. ;
Higashihara, M. ;
Takeda, K. ;
Fukutake, T. ;
Imafuku, I. ;
Mikata, T. ;
Shimizu, T. .
JOURNAL OF THE NEUROLOGICAL SCIENCES, 2009, 285 :S139-S139
[44]   Treatment for Lambert-Eaton myasthenic syndrome [J].
Maddison, P ;
Newsom-Davis, J .
COCHRANE DATABASE OF SYSTEMATIC REVIEWS, 2005, (02)
[45]   Antibodies to calcium channel and synaptotagmin in Lambert-Eaton myasthenic syndrome [J].
Takamori, M ;
Komai, K ;
Iwasa, K .
AMERICAN JOURNAL OF THE MEDICAL SCIENCES, 2000, 319 (04) :204-208
[46]   ANTIBODIES AGAINST CALCIUM CHANNELS IN THE LAMBERT-EATON MYASTHENIC SYNDROME [J].
WRAY, DW ;
LANG, B ;
NEWSOMDAVIS, J ;
PEERS, C .
CALCIUM CHANNELS : STRUCTURE AND FUNCTION, 1989, 560 :269-277
[47]   ANTIBODIES AGAINST CALCIUM CHANNELS IN THE LAMBERT-EATON MYASTHENIC SYNDROME [J].
WRAY, DW ;
LANG, B ;
NEWSOMDAVIS, J ;
PEERS, C .
ANNALS OF THE NEW YORK ACADEMY OF SCIENCES, 1989, 560 :269-277
[48]   Seronegative Lambert-Eaton myasthenic syndrome [J].
Nakao, YK ;
Motomura, M ;
Fukudome, T ;
Fukuda, T ;
Shiraishi, H ;
Yoshimura, T ;
Tsujihata, M ;
Eguchi, K .
NEUROLOGY, 2002, 59 (11) :1773-1775
[49]   Lambert-Eaton myasthenic syndrome in childhood [J].
Kostera-Pruszczyk, A. ;
Ryniewicz, B. ;
Rowinska-Marcinska, K. ;
Dutkiewicz, M. ;
Kaminska, A. .
EUROPEAN JOURNAL OF PAEDIATRIC NEUROLOGY, 2009, 13 (02) :194-196
[50]   Autonomic dysfunction in the Lambert-Eaton myasthenic syndrome - Serologic and clinical correlates [J].
O'Suilleabhain, P ;
Low, PA ;
Lennon, VA .
NEUROLOGY, 1998, 50 (01) :88-93