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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
Laboratory of Alternative Medicine and Experimental Therapeutics, Department of Clinical Pharmacy, Faculty of Pharmaceutical Sciences, Hokuriku University, Kanazawa, Japan
Department of Biophysical Genetics, Kanazawa University Graduate School of Medicine, Kanazawa, Japan
Neurological Center, Kanazawa Nishi Hospital, Kanazawa, Japan
Laboratory of Alternative Medicine and Experimental Therapeutics, Department of Clinical Pharmacy, Faculty of Pharmaceutical Sciences, Hokuriku University, 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
- 1 Laboratory of Alternative Medicine and Experimental Therapeutics, Department of Clinical Pharmacy, Faculty of Pharmaceutical Sciences, Hokuriku University, Kanazawa, Japan
- 2 Department of Biophysical Genetics, Kanazawa University Graduate School of Medicine, Kanazawa, Japan
- 3 Neurological Center, Kanazawa Nishi Hospital, Kanazawa, Japan
- 4 Laboratory of Alternative Medicine and Experimental Therapeutics, Department of Clinical Pharmacy, Faculty of Pharmaceutical Sciences, Hokuriku University, Kanazawa, Japan
- 5 Department of Neurology and Neurobiology of Aging, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan
- 6 Laboratory of Alternative Medicine and Experimental Therapeutics, Department of Clinical Pharmacy, Faculty of Pharmaceutical Sciences, Hokuriku University, Kanazawa, Japan
Advances in Bioscience and Biotechnology·Volume 04 (2013)·Pages 9–14·Published 13 June 2013·DOI10.4236/abb.2013.46A002
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Abstract
Autoantibody against neuronal nicotinic acetylcholine receptor (nAChR) α 3 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 α 3 subunits result in impairment of nicotine-evoked C a 2+ 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 α 3 subunits, and resulted in autonomic failure in AAG patients.
KeywordsNicotinic Acetylcholine Receptor <i>α</i>3 SubunitAntibodyEndocytosisCa<sup>2+</sup>InfluxAutoimmune Autonomic Ganglionopathy
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