Comparison between gentamycin and exon skipping treatments to restore ryanodine receptor subtype 2 functions in mdx mouse duodenum myocytes.

In Duchenne muscular dystrophy, a stop-codon mutation in the dystrophin gene induces an impairment of skeletal and smooth muscles contraction. In duodenum from mdx mouse, the disease model, the decrease of contractility was linked with the decrease of calcium signals encoded by ryanodine receptor subtype 2. Aminoglycoside and antisense oligonucleotide strategies were investigated to restore calcium signalling in the mdx mouse.

The decrease of expression of ryanodine receptor sub-type 2 is reversed by gentamycin sulphate in vascular myocytes from mdx mice.

The mdx mouse, a model of the human Duchenne muscular dystrophy, displays impaired contractile function in skeletal, cardiac and smooth muscles. We explored the possibility that ryanodine receptor (RYR) expression could be altered in vascular muscle. The three RYR sub-types were expressed in portal vein myocytes.

Acetylcholine evokes an InsP3R1-dependent transient Ca2+ signal in rat duodenum myocytes.

In smooth muscle myocytes, agonist-activated release of calcium ions (Ca2+) stored in the sarcoplasmic reticulum (SR) occurs via different but overlapping transduction pathways. Hence, to fully study how SR Ca2+ channels are activated, the simultaneous activation of different Ca2+ signals should be separated. In rat duodenum myocytes, we have previously characterized that acetylcholine (ACh) induces Ca2+ oscillations by binding to its M2 muscarinic receptor and activating the ryanodine receptor subtype 2.

Full length ryanodine receptor subtype 3 encodes spontaneous calcium oscillations in native duodenal smooth muscle cells.

Two isoforms of the ryanodine receptor subtype 3 (RYR3) have been described in smooth muscle. The RYR3 short isoform (RYR3S) negatively regulates the calcium-induced calcium release mechanism encoded by the RYR2, whereas the role of the full length isoform of RYR3 (RYR3L) was still unclear. Here, we describe RYR-dependent spontaneous Ca(2+) oscillations measured in 10% of native duodenum myocytes.

Acetylcholine-induced Ca2+ oscillations are modulated by a Ca2+ regulation of InsP3R2 in rat portal vein myocytes.

Oscillations of cytosolic Ca2+ levels are believed to have important roles in various metabolic and signalling processes in many cell types. Previously, we have demonstrated that acetylcholine (ACh) evokes Ca2+ oscillations in vascular myocytes expressing InsP3R1 and InsP3R2, whereas transient responses are activated in vascular myocytes expressing InsP3R1 alone. The molecular mechanisms underlying oscillations remain to be described in these native smooth muscle cells.