Human primary skeletal muscle cells express glutamate receptor GluR3, are activated by glutamate, and are affected by autoimmune GluR3B antibodies of epilepsy patients.

Background: Glutamate is the major excitatory neurotransmitter in the nervous system, common in neuromuscular junctions, and with abnormally reduced levels in several muscle diseases. Glutamate receptor AMPA GluR3, encoded by the GRIA3 gene, has important neurophysiological roles in regulation of neural networks, sleep, and breathing. GluR3 deletion or abnormal function increases the susceptibility to seizures and disrupts oscillatory networks of sleep, breathing, exploratory activity, and motor coordination. Questions: Do human skeletal muscle cells express GluR3? Are they activated by glutamate? Do autoimmune GluR3 Results: We discovered several original findings: 1) Human primary skeletal muscle cells (myoblasts) express GluR3 RNA and protein, evident by PCR and immunostaining, 2) glutamate (10 Possible implications: Together, the novel findings in this study may have various important implications on muscle physiology and pathology and call for continuation studies on diverse physiological, pathological and therapeutic topics. Meanwhile, we raise few hypotheses: 1) GluR3 has an important physiological role in muscle cells and motor function, 2) impaired GluR3 function (due to genetic/epigenetic/autoimmune/infectious/inflammatory factors?) can cause muscle impairments and motor problems, 3) glutamate, by direct activation of GluR3 and/or other GluRs expressed in skeletal muscle cells, can beneficially affect muscle cell survival, growth, and function, 3) Glutamate, iGluR agonists, and/or GluR3