Impaired Ca2+ release contributes to muscle weakness in a rat model of critical illness myopathy. Issue 1 (December 2016)

• Record Type: Journal Article
• Authors: Llano-Diez, Monica; Cheng, Arthur; Jonsson, William; Ivarsson, Niklas; Westerblad, Håkan; Sun, Vic; Cacciani, Nicola; Larsson, Lars; Bruton, Joseph
• Is Part Of: Critical care. Volume 20:Issue 1(2016)
• Page Start: 1
• Page End: 8
• Publication Date: 2016-12
• Subjects: Critical illness myopathy -- Intensive care unit -- Skeletal muscle weakness -- Ca2+ handling -- Excitation-contraction coupling; Critical care medicine -- Periodicals; 616.02805
• DOI: 10.1186/s13054-016-1417-z
• Languages: English
• ISSNs: 1364-8535

Abstract

Abstract Background Critical illness myopathy is an acquired skeletal muscle disorder with severe myosin loss and muscle weakness frequently seen in intensive care unit (ICU) patients. It is unknown if impaired excitation-contraction coupling contributes to the muscle weakness. Methods We used a unique ICU model where rats were deeply sedated, post-synaptically pharmacologically paralyzed, mechanically ventilated and closely monitored for up to ten days. Single intact fibers from the flexor digitorum brevis muscle were isolated and used to measure force and free myoplasmic [Ca2+ ] ([Ca2+ ]i ) during tetanic contractions. Results Fibers from ICU rats had 80 % lower tetanic [Ca2+ ]i and produced only 15 % of the force seen in fibers from sham-operated (SHAM) rats. In the presence of 5 mM caffeine, tetanic [Ca2+ ]i was similar in fibers from ICU and SHAM rats but force was 50 % lower in fibers from ICU rats than SHAM rats. Confocal imaging showed disrupted tetanic [Ca2+ ]i transients in fibers from ICU rats compared to SHAM rats. Western blots showed similar levels of Na+ channel and dihydropyridine receptor (DHPR) protein expression, whereas ryanodine receptor (RyR) and sarco-endoplasmic reticulum Ca2+ ATPase 1 (SERCA1) expression was markedly lower in muscle of ICU rats than in SHAM rats. Immunohistochemical analysis showed that distribution of Na+ channel and DHPR protein on the sarcolemma was disrupted in fibers from ICU rats compared with SHAM rats. Conclusions These results suggest that impaired SR Ca2+ release contributes to the muscle weakness seen in patients in ICU.