Ryanodine receptors are responsible for the massive release of calcium from the sarcoplasmic reticulum that triggers heart muscle contraction. Maurocalcin (MCa) is a 33 amino acid peptide toxin known to target skeletal ryanodine receptor. We investigated the effect of MCa and its analog MCaE12A on isolated cardiac ryanodine receptor (RyR2), and showed that they increase RyR2 sensitivity to cytoplasmic calcium concentrations promoting channel opening and decreases its sensitivity to inhibiting calcium concentrations. By measuring intracellular Ca2+ transients, calcium sparks and contraction on cardiomyocytes isolated from adult rats or differentiated from human-induced pluripotent stem cells, we demonstrated that MCaE12A passively penetrates cardiomyocytes and promotes the abnormal opening of RyR2. We also investigated the effect of MCaE12A on the pacemaker activity of sinus node cells from different mice lines and showed that, MCaE12A improves pacemaker activity of sinus node cells obtained from mice lacking L-type Cav1.3 channel, or following selective pharmacologic inhibition of calcium influx via Cav1.3. Our results identify MCaE12A as a high-affinity modulator of RyR2 and make it an important tool for RyR2 structure-to-function studies as well as for manipulating Ca2+ homeostasis and dynamic of cardiac cells.
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Chakraborti and colleagues (pp. 1345–1362) report the identification of bacteriophage ƛ NinH as a structural and functional analog of the bacterial nucleoid-associated protein Fis. NinH may influence phage excision-integration reactions or bacterial gene expression by competing with Fis for binding sites. The cover image shows Fis bound to DNA with homology to NinH highlighted. NinH binds and bends DNA with a preference for a 15 bp palindromic motif that is closely related to that recognised by E. coli Fis.
Maurocalcin and its analog MCaE12A facilitate Ca2+ mobilization in cardiomyocytes
Stephan De Waard, Jérome Montnach, Charly Cortinovis, Olfa Chkir, Morteza Erfanian, Philippe Hulin, Nathalie Gaborit, Patricia Lemarchand, Pietro Mesirca, Isabelle Bidaud, Matteo E. Mangoni, Michel De Waard, Michel Ronjat; Maurocalcin and its analog MCaE12A facilitate Ca2+ mobilization in cardiomyocytes. Biochem J 30 October 2020; 477 (20): 3985–3999. doi: https://doi.org/10.1042/BCJ20200206
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