Examining the functional effects of nitrosative stress on the ryanodine receptor and the contractile filaments from skeletal muscle

M. Steinz, M. Persson, N. Beard, D. Rassier, J. Lanner

Research output: Contribution to journalMeeting Abstractpeer-review

Abstract

Muscle weakness is a frequent complication in patients with rheumatoid arthritis. We have previously reported that muscle weakness in mice with arthritis (collagen-induced arthritis) was accompanied by increased peroxynitrite-derived nitrosative stress (nitration) on the ryanodine receptor (RyR1) and the contractile protein actin. However, the functional effects of nitration on RyR1 and the myofibrils are not fully understood. The aim of this study was to induce nitration using 5-amino-3-(4-morpholinyl)-1,2,3-oxadiazolium chloride (SIN-1) and examine gating properties of RyR1 and myofibrillar force production. Skeletal muscle homogenates from soleus muscle and extensor digitorum longus (EDL) were incubated with SIN-1, and nitration levels were then assessed with Western blot stained for 3-nitrotyrosine (3-NT). SIN-1 introduced a dose-dependent increase in the 3-NT signal with a half-maximum of ~ 5 mM SIN-1. Single RyR1 channel recordings in planar bilayers showed ~2.5-fold increase in RyR1 open probability in the presence of SIN-1 (1 mM). Force measurement of isolated myofibrils with atomic force cantilevers showed that incubation with SIN-1 (10 mM) results in a ~50% reduction in force production. To conclude, SIN-1 induced an increase in RyR1 open probability and decreased myofibrillar force, which indicates that nitration per se can alter Ca2+ release and skeletal muscle contractility. Further studies are needed to explain how nitration exerts its effects on RyR1 and myofilaments and how arthritis causes increased nitrosative load on these components in skeletal muscle.Can a brief, app-based mindfulness intervention reduce body dissatisfaction?
Original languageEnglish
Pages (from-to)29-29
Number of pages1
JournalActa Physiologica Scandinavica
Publication statusPublished - Feb 2017

Fingerprint

Dive into the research topics of 'Examining the functional effects of nitrosative stress on the ryanodine receptor and the contractile filaments from skeletal muscle'. Together they form a unique fingerprint.

Cite this