Decreased intracellular [Ca 2+ ] coincides with reduced expression of Dhprα1s, RyR1, and diaphragmatic dysfunction in a rat model of sepsis

Muscle Nerve. 2017 Dec;56(6):1128-1136. doi: 10.1002/mus.25554. Epub 2017 Mar 23.

Abstract

Introduction: Sepsis can cause decreased diaphragmatic contractility. Intracellular calcium as a second messenger is central to diaphragmatic contractility. However, changes in intracellular calcium concentration ([Ca2+ ]) and the distribution and co-localization of relevant calcium channels [dihydropyridine receptors, (DHPRα1s) and ryanodine receptors (RyR1)] remain unclear during sepsis. In this study we investigated the effect of changed intracellular [Ca2+ ] and expression and distribution of DHPRα1s and RyR1 on diaphragm function during sepsis.

Methods: We measured diaphragm contractility and isolated diaphragm muscle cells in a rat model of sepsis. The distribution and co-localization of DHPRα1s and RyR1 were determined using immunohistochemistry and immunofluorescence, whereas intracellular [Ca2+ ] was measured by confocal microscopy and fluorescence spectrophotometry.

Results: Septic rat diaphragm contractility, expression of DHPRα1s and RyR1, and intracellular [Ca2+ ] were significantly decreased in the rat sepsis model compared with controls.

Discussion: Decreased intracellular [Ca2+ ] coincides with diaphragmatic contractility and decreased expression of DHPRα1s and RyR1 in sepsis. Muscle Nerve 56: 1128-1136, 2017.

Keywords: DHPRα1s; RyR1; diaphragm; intracellular [Ca2+]; sepsis.

MeSH terms

  • Animals
  • Calcium / metabolism*
  • Calcium Channels, L-Type / biosynthesis*
  • Calcium Channels, L-Type / genetics
  • Diaphragm / metabolism*
  • Diaphragm / physiopathology
  • Gene Expression
  • Intracellular Fluid / metabolism*
  • Male
  • Muscle Contraction / physiology
  • Organ Culture Techniques
  • Rats
  • Rats, Sprague-Dawley
  • Ryanodine Receptor Calcium Release Channel / biosynthesis*
  • Ryanodine Receptor Calcium Release Channel / genetics
  • Sepsis / genetics
  • Sepsis / metabolism*
  • Sepsis / physiopathology

Substances

  • CACNA1S protein, mouse
  • Calcium Channels, L-Type
  • Ryanodine Receptor Calcium Release Channel
  • Calcium