Attenuation of nicotine-evoked Ca<sup>2+</sup>influx by antibody to the nicotinic acetylcholine receptor <i>α</i>3 subunits in human embryonic kidney cells

作     者：Shota Kobayashi Shigeru Yokoyama Takahiro Maruta Akiko Muroyama Hiroaki Yoshikawa Yasuhide Mitsumoto 

作者机构：Department of Biophysical Genetics Kanazawa University Graduate School of Medicine Kanazawa Japan Department of Neurology and Neurobiology of Aging Kanazawa University Graduate School of Medical Science Kanazawa Japan Laboratory of Alternative Medicine and Experimental Therapeutics Department of Clinical Pharmacy Faculty of Pharmaceutical Sciences Hokuriku University Kanazawa Japan Neurological Center Kanazawa Nishi Hospital Kanazawa Japan 

出 版 物：《Advances in Bioscience and Biotechnology》 (生命科学与技术进展（英文）)

年 卷 期：2013年第4卷第6期

页      面：9-14页

学科分类：1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学] 

主　　题：Nicotinic Acetylcholine Receptor α3 Subunit Antibody Endocytosis Ca2+ Influx Autoimmune Autonomic Ganglionopathy 

摘      要：Autoantibody against neuronal nicotinic acetylcholine receptor (nAChR) α3 subunit is implicated in severe autonomic dysfunction in the patients with autoimmune autonomic ganglionopathy (AAG). Although this autoantibody has been revealed to impair fast excitatory synaptic transmission in autonomic ganglia, its precise mechanism remains unknown. Here, we show that antibody-induced reduction of cell-surface α3 subunits result in impairment of nicotine-evoked Ca2+ influx in stably transfected human embryonic kidney cells. These effects of the antibody were remarkably inhibited by interfering with the endocytic machinery at low-temperature. We conclude that reduction of nAChR in autonomic ganglia can be mediated by the endocytosis of α3 subunits, and resulted in autonomic failure in AAG patients.