Nerve-dependent distribution of subsynaptic type 1 inositol 1,4,5-trisphosphate receptor at the neuromuscular junction

Abstract

Inositol 1,4,5-trisphosphate receptors (IP3Rs) are enriched at postsynaptic membrane compartments of the neuromuscular junction (NMJ), surrounding the subsynaptic nuclei and close to nicotinic acetylcholine receptors (nAChRs) of the motor endplate. At the endplate level, it has been proposed that nerve-dependent electrical activity might trigger IP3-associated, local Ca2+ signals not only involved in excitation–transcription (ET) coupling but also crucial to the development and stabilization of the NMJ itself. The present study was undertaken to examine whether denervation affects the subsynaptic IP3R distribution in skeletal muscles and which are the underlying mechanisms. Fluorescence microscopy, carried out on in vivo denervated muscles (following sciatectomy) and in vitro denervated skeletal muscle fibers from flexor digitorum brevis (FDB), indicates that denervation causes a reduction in the subsynaptic IP3R1-stained region, and such a decrease appears to be determined by the lack of muscle electrical activity, as judged by partial reversal upon field electrical stimulation of in vitro denervated skeletal muscle fibers.

Early Alterations in Structural and Functional Properties in the Neuromuscular Junctions of Mutant FUS Mice

“…Accordingly, a decrease in external Ca 2+ concentration could remove the inhibition of nAChRs in ∆FUS(1-359) mice. Note that Ca 2+ influx through nAChR can activate inositol 1,4,5-trisphosphate receptors enriched in the postsynaptic compartment surrounding the subsynaptic nuclei, and this calcium signaling is crucial to the stabilization of NMJs [48,54]. Hence, the suppression of currents via nAChRs at the pre-onset stage might be a reason for NMJ disorganization in ∆FUS(1-359) mice at the later stage.…”