Author(s)

Shota Kobayashi, Shigeru Yokoyama, Takahiro Maruta, Akiko Muroyama, Hiroaki Yoshikawa, Yasuhide Mitsumoto

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.

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.

Nicotinic Acetylcholine Receptor α3 Subunit; Antibody; Endocytosis; Ca²⁺ Influx; Autoimmune Autonomic Ganglionopathy

Kobayashi, S. , Yokoyama, S. , Maruta, T. , Muroyama, A. , Yoshikawa, H. and Mitsumoto, Y. (2013) Attenuation of nicotine-evoked Ca²⁺ influx by antibody to the nicotinic acetylcholine receptor α3 subunits in human embryonic kidney cells. Advances in Bioscience and Biotechnology, 4, 9-14. doi: 10.4236/abb.2013.46A002.