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

Author:

Volpe Pompeo1ORCID,Bosutti Alessandra2,Nori Alessandra1ORCID,Filadi Riccardo13,Gherardi Gaia1,Trautmann Gabor4ORCID,Furlan Sandra3ORCID,Massaria Gabriele2,Sciancalepore Marina2ORCID,Megighian Aram1ORCID,Caccin Paola1,Bernareggi Annalisa2,Salanova Michele45ORCID,Sacchetto Roberta6ORCID,Sandonà Dorianna1ORCID,Pizzo Paola13,Lorenzon Paola2ORCID

Affiliation:

1. Department of Biomedical Sciences and Interdepartmental Research Center of Myology (cirMYO), University of Padova, Padova, Italy 1

2. Department of Life Sciences, University of Trieste, Trieste, Italy 2

3. National Research Council, Neuroscience Institute, Padova, Italy 3

4. Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Institute of Integrative Neuroanatomy, Berlin, Germany 4

5. Neuromuscular Signaling, Center of Space Medicine Berlin, Berlin, Germany 5

6. Department of Comparative Biomedicine and Food Science, University of Padova, Padova, Italy 6

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.

Funder

ASI NEMUCO

Publisher

Rockefeller University Press

Subject

Physiology

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