BACKGROUND The formation of acetylcholine receptor (AChR) cluster is a key event during the development of the neuromuscular junction. It is induced through the activation of muscle-specific kinase (MuSK) by the heparan-sulfate proteoglycan agrin released from the motor axon. On the other hand, DC electric field, a non-neuronal stimulus, is also highly effective in causing AChRs to cluster alon...

Motor neurons regulate the acetylcholine sensitivity of the muscles they innervate: denervated muscle fiber become "supersensitive" to acetylcholine, due to insertion of newly synthesized acetylcholine receptors (AChRs) in the plasma membrane. We used hybridization analysis with a cloned cDNA specific for AChR alpha-subunit to compare the abundance of AChR mRNA in innervated and denervated adul...

Myasthenia gravis (MG) is an autoimmune disease of the neuromuscular junction, where acetylcholine receptor (AChR), muscle-specific kinase (MuSK), and low-density lipoprotein (LDL) receptor-related protein 4 (Lrp4) are essential. About 80% and 0% to 10% of patients with generalized MG have autoantibodies to AChR and MuSK, respectively, but pathogenic factors are elusive in others. Here we show ...

The nicotinic acetylcholine receptor (AChR) is a large membrane protein found in muscle cells. It is involved in the transformation of acetylcholine packets into a membrane depolarization, which thereby leads to a muscle twitch. This large, complex molecule is the target of the autoimmune attack in myasthenia gravis, and much has been learned in the past decade about myasthenia by the induction...

Cells from a line of transformed quail fibroblasts (QT-6) were transfected with cDNAs coding for subunits of the mouse muscle nicotinic ACh receptor (AChR). Stable clones were selected that expressed subunits of the fetal-type AChR (alpha, beta, gamma, delta) or the adult-type AChR (alpha, beta, epsilon, delta). The receptors had the appropriate burst durations and single-channel conductances f...

Nicotinic acetylcholine receptors (AChR) are ligand-gated cation channels that are present throughout the nervous system. The ganglionic (alpha3-type) neuronal AChR mediates fast synaptic transmission in sympathetic, parasympathetic and enteric autonomic ganglia. Autonomic ganglia are an important site of neural integration and regulation of autonomic reflexes. Impaired cholinergic ganglionic s...

Although the dissociative anesthetic dizocilpine [(+)-MK-801] inhibits nicotinic acetylcholine receptor (AChR) function in a noncompetitive manner, the location of the dizocilpine binding site(s) has yet to be clearly established. Thus, to characterize the binding site for dizocilpine on the AChR we examined 1) the dissociation constant (K(d)) and stoichiometry of [(3)H]dizocilpine binding; 2) ...

CollagenQ (ColQ) plays an important structural role at vertebrate neuromuscular junctions (NMJs) by anchoring and accumulating acetylcholinesterase (AChE) in the extracellular matrix (ECM). Moreover, ColQ interacts with perlecan/dystroglycan and the muscle-specific receptor tyrosine kinase (MuSK), key molecules in the NMJ formation. MuSK promotes acetylcholine receptor (AChR) clustering in a pr...

The class of diterpenoids with a 14-carbon cembrane ring, the cembranoids, includes both competitive and noncompetitive inhibitors of the nicotinic acetylcholine receptor (AChR). All 20 coelenterate-derived cembranoids studied in this report inhibited [piperidyl-3,4-3H]-phencyclidine ([3H]-PCP) binding to its high-affinity site on the electric organ AChR, with IC50s ranging from 0.9 microM for ...

In cultured chicken myotubes, calcitonin gene-related peptide (CGRP), a peptide present in spinal cord motoneurons, increased by 1.5-fold the number of surface acetylcholine receptors (AChRs) and by threefold AChR alpha-subunit mRNA level without affecting the level of muscular alpha-actin mRNA. Cholera toxin (CT), an activator of adenylate cyclase, produced a similar effect, which did not add ...