Differential effects of maurocalcine on Ca2+ release events and depolarization-induced Ca2+ release in rat skeletal muscle

Henrietta Szappanos, Sophia Smida-Rezgui, Julianna Cseri, Cecilia Simut, Jean Marc Sabatier, Michel De Waard, László Kovács, László Csernoch, Michel Ronjat

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Maurocalcine (MCa), a 33 amino acid toxin obtained from scorpion venom, has been shown to interact with the isolated skeletal-type ryanodine receptor (RyR1) and to strongly modify its calcium channel gating. In this study, we explored the effects of MCa on RyR1 in situ to establish whether the functional interaction of RyR1 with the voltage-sensing dihydropyridine receptor (DHPR) would modify the ability of MCa to interact with RyR1. In developing skeletal muscle cells the addition of MCa into the external medium induced a calcium transient resulting from RyR1 activation and strongly inhibited the effect of the RyR1 agonist chloro-m-cresol. In contrast, MCa failed to affect the depolarization-induced Ca2+ release. In intact adult fibres MCa did not induce any change in the cytosolic Ca2+ concentration. However, when the surface membrane was permeabilized and calcium release events were readily observable, MCa had a time-dependent dual effect: it first increased event frequency, from 0.060 ± 0.002 to 0.150 ± 0.007 sarcomere-1 s-1, and reduced the amplitude of individual events without modifying their spatial distribution. Later on it induced the appearance of long-lasting events resembling the embers observed in control conditions but having a substantially longer duration. We propose that the functional coupling of DHPRs and RyR1 s within a Ca2+ release unit prevents MCa from either reaching its binding site or from being able to modify the gating not only of the RyR1s physically coupled to DHPRs but all RyR1s within the Ca2+ release unit.

Original languageEnglish
Pages (from-to)843-853
Number of pages11
JournalJournal of Physiology
Issue number3
Publication statusPublished - Jun 15 2005

ASJC Scopus subject areas

  • Physiology

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    Szappanos, H., Smida-Rezgui, S., Cseri, J., Simut, C., Sabatier, J. M., De Waard, M., Kovács, L., Csernoch, L., & Ronjat, M. (2005). Differential effects of maurocalcine on Ca2+ release events and depolarization-induced Ca2+ release in rat skeletal muscle. Journal of Physiology, 565(3), 843-853. https://doi.org/10.1113/jphysiol.2005.086074