Passive transfer of Lambert-Eaton myasthenic syndrome induces dihydropyridine sensitivity of ICa in mouse motor nerve terminals.
Passive transfer of Lambert-Eaton myasthenic syndrome induces dihydropyridine sensitivity of ICa in mouse motor nerve terminals.
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Lambert-Eaton肌无力综合征的被动转移诱导小鼠运动神经末梢ICa的二氢吡啶敏感性。
DOI：
10.1152/jn.1998.80.3.1056
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发表时间：
1998
影响因子：
2.5
通讯作者：
W. Atchison
中科院分区：
文献类型：
--
作者：
Y. F. Xu;S. Hewett;W. Atchison
小鼠被注射来自三名兰伯特-伊顿肌无力综合症（LEMS）患者的血浆30天。从胸骨三角肌制剂的运动轴突末端的神经束膜进行记录。目的是从药理学角度表征与受 LEMS 自身抗体影响的运动神经末梢 Ca2+ 电流 (ICa) 相关的动力学上不同的、确定的电位变化的特性。在 LEMS 处理的神经末梢中，0.01 Hz 引发的 ICa 振幅显着降低，约为对照的 35%。在 10 Hz 刺激期间，LEMS 处理的运动神经末梢的 ICa 幅度没有变化，但在对照组中则降低。在 20 或 100 Hz 训练期间，经 LEMS 处理的神经末梢发生 ICa 促进作用，而在对照中，20 Hz 训练期间没有发生促进作用，而在 100 Hz 频率下发生明显抑制。对照终端中 ICa 的振幅和持续时间分别在 2 和 4-6 mM 细胞外 Ca2+ 时达到饱和；在 LEMS 处理的终端中，细胞外 Ca2+ 浓度必须增加对照的两到三倍才能达到饱和。当制剂暴露于 50 µM 3,4-二氨基吡啶和 1 mM 四乙铵时观察到的 ICa 两种成分的振幅均因 LEMS 等离子体处理而降低。快成分 (ICa,s) 减少了 35%，而慢成分 (ICa,s) 减少了 37%。 omega-Agatoxin IVA (omega-Aga-IVA; 0.15 microM) 和 omega-conotoxin-MVIIC (omega-CTx-MVIIC; 5 microM) 完全阻断控制运动神经末梢中的 ICa。相同浓度的毒素在 LEMS 处理的终端中阻断 ICa 的效果要低 20-30%。用 omega-Aga-IVA 或 omega-CTx-MVIIC 治疗后剩余的残留 ICa 被 10 microM 硝苯地平和 10 microM Cd2+ 阻断。因此，LEMS 血浆似乎下调小鼠运动神经末梢中的 omega-Aga-IVA 敏感（P 型）和/或 omega-CTx-MVIIC 敏感（Q 型）Ca2+ 通道，而二氢吡啶（DHP）敏感（L 型）Ca2+ 通道在这些终端中未被掩盖。与用同等浓度的对照 Igs 孵育的突触体相比，大鼠前脑突触体急性暴露于 LEMS 免疫球蛋白（Igs；4 mg/ml）（90 分钟）不会改变 [3H]-尼群地平或 [125I]-omega-芋螺毒素-GVIA (-omega-CgTx GVIA) 的结合。相反，LEMS Igs 显着降低 [3H]-维拉帕米的 Bmax 至对照的约 45%。维拉帕米 (KD) 对其余受体的表观亲和力没有显着改变。因此，分离的中枢神经末梢急性暴露于 LEMS Igs 不会增加 DHP 敏感性，而会减少维拉帕米的结合位点数量，但不会减少尼群地平或 omega-CgTx-GVIA 的结合位点数量。这些结果表明，长期而不是急性暴露于 LEMS Igs 会上调或暴露运动神经末梢中 DHP 敏感的 Ca2+ 通道。
Mice were injected for 30 days with plasma from three patients with Lambert-Eaton Myasthenic Syndrome (LEMS). Recordings were made from the perineurial sheath of motor axon terminals of triangularis sterni muscle preparations. The objective was to characterize pharmacologically the identity of kinetically distinct, defined potential changes associated with motor nerve terminal Ca2+ currents (ICa) that were affected by LEMS autoantibodies. ICa elicited at 0.01 Hz were significantly reduced in amplitude by approximately 35% of control in LEMS-treated nerve terminals. During 10-Hz stimulation, ICa amplitude was unchanged in LEMS-treated motor nerve terminals, but was depressed in control. During 20- or 100-Hz trains, facilitation of ICa occurred in LEMS-treated nerve terminals whereas in control, no facilitation occurred during the trains at 20 Hz and marked depression occurred at 100 Hz. Saturation for amplitude and duration of ICa in control terminals occurred at 2 and 4-6 mM extracellular Ca2+, respectively; in LEMS-treated terminals, the extracellular Ca2+ concentration had to increase by two to three times of control to cause saturation. Amplitude of the two components of ICa observed when the preparation was exposed to 50 microM 3,4-diaminopyridine and 1 mM tetraethylammonium were both reduced by LEMS plasma treatment. The fast component (ICa,s) was reduced by 35%, whereas the slow component (ICa, s) was reduced by 37%. omega-Agatoxin IVA (omega-Aga-IVA; 0.15 microM) and omega-conotoxin-MVIIC (omega-CTx-MVIIC; 5 microM) completely blocked ICa in control motor nerve terminals. The same concentrations of toxins were 20-30% less effective in blocking ICa in LEMS-treated terminals. The residual ICa remaining after treatment with omega-Aga-IVA or omega-CTx-MVIIC was blocked by 10 microM nifedipine and 10 microM Cd2+. Thus LEMS plasma appears to downregulate omega-Aga-IVA-sensitive (P-type) and/or omega-CTx-MVIIC-sensitive (Q-type) Ca2+ channels in murine motor nerve terminals, whereas dihydropyridine (DHP)-sensitive (L-type) Ca2+ channels are unmasked in these terminals. Acute exposure (90 min) of rat forebrain synaptosomes to LEMS immunoglobulins (Igs; 4 mg/ml) did not alter the binding of [3H]-nitrendipine or [125I]-omega-conotoxin-GVIA (-omega-CgTx GVIA) when compared with synaptosomes incubated with an equivalent concentration of control Igs. Conversely, LEMS Igs significantly decreased the Bmax for [3H]-verapamil to approximately 45% of control. The apparent affinity of verapamil (KD) for the remaining receptors was not significantly altered. Thus acute exposure of isolated central nerve terminals to LEMS Igs does not increase DHP sensitivity, whereas it reduces the number of binding sites for verapamil but not for nitrendipine or omega-CgTx-GVIA. These results suggest that chronic but not acute exposure to LEMS Igs either upregulates or unmasks DHP-sensitive Ca2+ channels in motor nerve endings.
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DOI：
--
发表时间：
1984
期刊：
The Journal of pharmacology and experimental therapeutics
影响因子：
--
作者：
Boles,RG;Yamamura,HI;Schoemaker,H;Roeske,WR
通讯作者：
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DOI：
--
发表时间：
1996
期刊：
The Journal of pharmacology and experimental therapeutics
影响因子：
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作者：
Xu,YF;Atchison,WD
通讯作者：
Atchison,WD
影响因子：
158.5
作者：
LENNON, VA;KRYZER, TJ;LAMBERT, EH
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LAMBERT, EH
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DOI：
--
发表时间：
1989
期刊：
The Journal of pharmacology and experimental therapeutics
影响因子：
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作者：
Atchison,WD
通讯作者：
Atchison,WD
P 型电压依赖性钙通道介导哺乳动物突触中的突触前钙流入和递质释放。
DOI：
10.1073/pnas.89.8.3330
发表时间：
1992
影响因子：
11.1
作者：
Uchitel,OD;Protti,DA;Sanchez,V;Cherksey,BD;Sugimori,M;Llinás,R
通讯作者：
Llinás,R