[Basic and clinical importance of nicotinic acetylcholine receptors].
Shortly after encountering the muscle surface, the motor axon releases agrin to the postsynaptic muscle membrane to regulate postsynaptic differentiation. Neural agrin activates postsynaptic muscle-specific kinase to induce aggregation of muscle nicotinic acetylcholine receptors (nAChR) expressed throughout the muscle surface into the subsynaptic area. Agrin also regulates the distribution of other synaptic proteins, including rapsyn, ErbB receptor. Rapsyn, 43-kd cytoplasmic protein, attaches to the beta subunit of synaptic nAChR and anchors it at the neuromuscular junction. Neureglin binds to ErbB receptors to activate a pathway that leads to enhance mature nAChR gene transcription in synaptic nuclei. While, a voltage change evoked by binding of acetylcholine to nAChR leads to down-regulate fetal nAChR expression in extrasynaptic nuclei. Denervation causes destruction of normal neuromuscular synapse and induces up-regulation of immature nAChR at extrajunctional sites. Importantly in clinical settings, the immature nAChR is resistant to non-depolarizing neuromuscular blocking agents and more sensitive to depolarizing muscle relaxants.
Suzuki
Takahiro
T
Department of Anesthesiology, Surugadai Nihon University Hospital, Tokyo 101-8309.
D018171:Agrin / Q000502:physiology; D000818:Animals; D006801:Humans; D007008:Hypokalemia / Q000209:etiology; D009124:Muscle Proteins / Q000378:metabolism; D020880:Neuregulins / Q000502:physiology; D009467:Neuromuscular Depolarizing Agents / Q000494:pharmacology; D009469:Neuromuscular Junction / Q000378:metabolism; D003473:Neuromuscular Nondepolarizing Agents / Q000494:pharmacology; D011485:Protein Binding; D011978:Receptors, Nicotinic / Q000187:drug effects / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D013569:Synapses; D014158:Transcription, Genetic; D015854:Up-Regulation
D018171:Agrin; D009124:Muscle Proteins; D020880:Neuregulins; D009467:Neuromuscular Depolarizing Agents; D003473:Neuromuscular Nondepolarizing Agents; D011978:Receptors, Nicotinic; C051609:peripheral membrane protein 43K