HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 584/1/47    most recent jphysiol.2007.137687v1 Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Avila, G. Articles by Ramos-Mondragón, R. Search for Related Content PubMed PubMed Citation Articles by Avila, G. Articles by Ramos-Mondragón, R. Related Collections Cellular

¹ Departamento de Bioquímica, Cinvestav-IPN, AP 14-740, México, DF 07000, México

We investigated modulation of excitation–contraction (EC) coupling by calcitonin gene-related peptide (CGRP), which is released by motorneurons during neuromuscular transmission. Mouse skeletal myotubes were cultured either under control conditions or in the presence of 100 nM CGRP (4–72 h). T- and L-type Ca²⁺ currents, immobilization resistant charge movement, and intracellular Ca²⁺ transients were characterized in whole-cell patch-clamp experiments. CGRP treatment increased the amplitude of voltage-gated Ca²⁺ release ((F/F)_max) 75–350% and moderately increased both maximal L-current conductance (G_max) and charge movement (Q_max). In contrast, CGRP treatment did not affect their corresponding voltage dependence of activation (V_1/2 and k) or T-current density. CGRP treatment enhanced voltage-gated Ca²⁺ release in 4 h, whereas the effect on L-channel magnitude took longer to develop (24 h), suggesting that short-term potentiation of EC coupling may lead to subsequent long-term up-regulation of DHPR expression. CGRP treatment also drastically increased caffeine-induced Ca²⁺ release in 4 h (400%). Thus, short-term potentiation of EC coupling is due to an increase in sarcoplasmic reticulum Ca²⁺ content. Both application of a phosphodiesterase inhibitor (papaverine) and a membrane-permeant cAMP analogue (Db-cAMP) produced a similar potentiation of EC coupling. Conversely, this potentiation was prevented by pretreatment with either CGRP1 receptor antagonist (CGRP_8-37) or a PKA inhibitor (H-89). Thus, CGRP acts through CGRP1 receptors and the cAMP/PKA signalling pathway to enhance voltage-gated Ca²⁺ release. Effects of CGRP on both EC coupling and L-channels were attenuated at later times during myotube differentiation. Therefore, we conclude that CGRP accelerates maturation of EC coupling.

(Received 30 May 2007; accepted after revision 25 July 2007; first published online 26 July 2007)
Corresponding author G. Avila: Departamento de Bioquímica, Cinvestav-IPN, AP 14–740, México, DF 07000, México. Email: gavila{at}cinvestav.mx