Mosier D R, Baldelli P, Delbono O, Smith R G, Alexianu M E, Appel S H, Stefani E
Department of Neurology, Baylor College of Medicine, Houston, TX 77030.
Ann Neurol. 1995 Jan;37(1):102-9. doi: 10.1002/ana.410370119.
The sporadic form of amyotrophic lateral sclerosis (ALS) is an idiopathic and eventually lethal disorder causing progressive degeneration of cortical and spinal motoneurons. Recent studies have shown that the majority of patients with sporadic ALS have serum antibodies that bind to purified L-type voltage-gated calcium channels and that antibody titer correlates with the rate of disease progression. Furthermore, antibodies purified from ALS patient sera have been found to alter the physiologic function of voltage-gated calcium channels in nonmotoneuron cell types. Using whole-cell patch-clamp techniques, immunoglobulins purified from sera of 5 of 6 patients with sporadic ALS are now shown to increase calcium currents in a hybrid motoneuron cell line, VSC4.1. These calcium currents are blocked by the polyamine funnel-web spider toxin FTX, which has previously been shown to block Ca2+ currents and evoked transmitter release at mammalian motoneuron terminals. These data provide additional evidence linking ALS to an autoimmune process and suggest that antibody-induced increases in calcium entry through voltage-gated calcium channels may occur in motoneurons in this disease, with possible deleterious effects in susceptible neurons.
散发性肌萎缩侧索硬化症（ALS）是一种特发性且最终致命的疾病，会导致皮质和脊髓运动神经元进行性退化。最近的研究表明，大多数散发性ALS患者的血清抗体能与纯化的L型电压门控钙通道结合，且抗体滴度与疾病进展速度相关。此外，已发现从ALS患者血清中纯化出的抗体可改变非运动神经元细胞类型中电压门控钙通道的生理功能。运用全细胞膜片钳技术，现已表明从6例散发性ALS患者中的5例血清中纯化出的免疫球蛋白可增加杂交运动神经元细胞系VSC4.1中的钙电流。这些钙电流被多胺漏斗网蜘蛛毒素FTX阻断，此前已证明该毒素可阻断哺乳动物运动神经元终末的Ca2+电流并诱发递质释放。这些数据为将ALS与自身免疫过程联系起来提供了更多证据，并表明在该疾病中，运动神经元可能会出现抗体诱导的通过电压门控钙通道的钙内流增加，这可能会对易感神经元产生有害影响。
