Maurocalcine interacts with the cardiac ryanodine receptor without inducing channel modification

Xavier Altafaj, Julien France, Janos Almassy, I. Jóna, Daniela Rossi, Vincenzo Sorrentino, Kamel Mabrouk, Michel De Waard, Michel Ronjat

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

We have previously shown that MCa (maurocalcine), a toxin from the venom of the scorpion Maurus palmatus, binds to RyR1 (type 1 ryanodine receptor) and induces strong modifications of its gating behaviour. In the present study, we investigated the ability of MCa to bind to and modify the gating process of cardiac RyR2. By performing pull-down experiments we show that MCa interacts directly with RyR2 with an apparent affinity of 150 nM. By expressing different domains of RyR2 in vitro, we show that MCa binds to two domains of RyR2, which are homologous with those previously identified on RyR1. The effect of MCa binding to RyR2 was then evaluated by three different approaches: (i) [ 3H]ryanodine binding experiments, showing a very weak effect of MCa (up to 1 μM), (ii) Ca2+ release measurements from cardiac sarcoplasmic reticulum vesicles, showing that MCa up to 1 μM is unable to induce Ca2+ release, and (iii) single-channel recordings, showing that MCa has no effect on the open probability or on the RyR2 channel conductance level. Long-lasting opening events of RyR2 were observed in the presence of MCa only when the ionic current direction was opposite to the physiological direction, i.e. from the cytoplasmic face of RyR2 to its luminal face. Therefore, despite the conserved MCa binding ability of RyR1 and RyR2, functional studies show that, in contrast with what is observed with RyR1, MCa does not affect the gating properties of RyR2. These results highlight a different role of the MCa-binding domains in the gating process of RyR1 and RyR2.

Original languageEnglish
Pages (from-to)309-315
Number of pages7
JournalBiochemical Journal
Volume406
Issue number2
DOIs
Publication statusPublished - Sep 1 2007

Fingerprint

Ryanodine Receptor Calcium Release Channel
maurocalcine
Scorpion Venoms
Ryanodine
Sarcoplasmic Reticulum

Keywords

  • Calcium channel
  • Excitation-contraction coupling
  • Heart
  • Maurocalcine
  • Ryanodine receptor
  • Toxin

ASJC Scopus subject areas

  • Biochemistry

Cite this

Altafaj, X., France, J., Almassy, J., Jóna, I., Rossi, D., Sorrentino, V., ... Ronjat, M. (2007). Maurocalcine interacts with the cardiac ryanodine receptor without inducing channel modification. Biochemical Journal, 406(2), 309-315. https://doi.org/10.1042/BJ20070453

Maurocalcine interacts with the cardiac ryanodine receptor without inducing channel modification. / Altafaj, Xavier; France, Julien; Almassy, Janos; Jóna, I.; Rossi, Daniela; Sorrentino, Vincenzo; Mabrouk, Kamel; De Waard, Michel; Ronjat, Michel.

In: Biochemical Journal, Vol. 406, No. 2, 01.09.2007, p. 309-315.

Research output: Contribution to journalArticle

Altafaj, X, France, J, Almassy, J, Jóna, I, Rossi, D, Sorrentino, V, Mabrouk, K, De Waard, M & Ronjat, M 2007, 'Maurocalcine interacts with the cardiac ryanodine receptor without inducing channel modification', Biochemical Journal, vol. 406, no. 2, pp. 309-315. https://doi.org/10.1042/BJ20070453
Altafaj, Xavier ; France, Julien ; Almassy, Janos ; Jóna, I. ; Rossi, Daniela ; Sorrentino, Vincenzo ; Mabrouk, Kamel ; De Waard, Michel ; Ronjat, Michel. / Maurocalcine interacts with the cardiac ryanodine receptor without inducing channel modification. In: Biochemical Journal. 2007 ; Vol. 406, No. 2. pp. 309-315.
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