Free radicals and calcium homeostasis

relevance to malignant hyperthermia?

Garry G Duthie, John R Arthur

Research output: Contribution to journalLiterature review

12 Citations (Scopus)

Abstract

The regulation of intracellular free calcium ions (Ca2+) in skeletal muscle at rest and during contraction depends on mechanisms such as Na+-Ca2+ exchangers. Ca2+-ATPases, and the voltage-sensitive ryanodine receptor. The susceptibility of these regulatory mechanisms to free-radical-mediated damage may be increased because of their location within the lipid membranes of sarcolemma, sarcoplasmic reticulum, and mitochondrion with resultant uncontrolled increases in myoplasmic Ca2+ concentration and cell death. The potentially fatal pharmacogenetic disorder, malignant hyperthermia (MH), is characterised by muscle rigidity, arrythmias, lactic acidosis, and a rapid rise in body temperature. The sequence of events responsible for the MH syndrome remains uncertain, but it has been variously ascribed to faults in many of the Ca2+ regulatory mechanisms. In swine the condition is associated with a specific mutation in the ryanodine receptor, whereas in humans the syndrome is genetically heterogenous. Free-radical-mediated peroxidation of membrane lipids and proteins also results in the rapid efflux of Ca2+ from organelles, and the detection of products of free radical reactions in tissue from MH-susceptible individuals using electron spin resonance spectroscopy provides evidence for the involvement of free radicals in the MH syndrome.

Original languageEnglish
Pages (from-to)435-442
Number of pages8
JournalFree Radical Biology and Medicine
Volume14
Issue number4
DOIs
Publication statusPublished - Apr 1993

Keywords

  • free radical
  • malignant hyperthermia
  • calcium regulation
  • stress-susceptible pigs
  • pyruvate-kinase activity
  • h-3 ryanodine binding
  • free fatty-acids
  • sarcoplasmic-reticulum
  • skeletal-muscle
  • vitamin-E
  • lipid-peroxidation
  • release channel
  • glucose-6-phosphate-dehydrogenase deficiency

Cite this

Free radicals and calcium homeostasis : relevance to malignant hyperthermia? / Duthie, Garry G; Arthur, John R.

In: Free Radical Biology and Medicine, Vol. 14, No. 4, 04.1993, p. 435-442.

Research output: Contribution to journalLiterature review

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AB - The regulation of intracellular free calcium ions (Ca2+) in skeletal muscle at rest and during contraction depends on mechanisms such as Na+-Ca2+ exchangers. Ca2+-ATPases, and the voltage-sensitive ryanodine receptor. The susceptibility of these regulatory mechanisms to free-radical-mediated damage may be increased because of their location within the lipid membranes of sarcolemma, sarcoplasmic reticulum, and mitochondrion with resultant uncontrolled increases in myoplasmic Ca2+ concentration and cell death. The potentially fatal pharmacogenetic disorder, malignant hyperthermia (MH), is characterised by muscle rigidity, arrythmias, lactic acidosis, and a rapid rise in body temperature. The sequence of events responsible for the MH syndrome remains uncertain, but it has been variously ascribed to faults in many of the Ca2+ regulatory mechanisms. In swine the condition is associated with a specific mutation in the ryanodine receptor, whereas in humans the syndrome is genetically heterogenous. Free-radical-mediated peroxidation of membrane lipids and proteins also results in the rapid efflux of Ca2+ from organelles, and the detection of products of free radical reactions in tissue from MH-susceptible individuals using electron spin resonance spectroscopy provides evidence for the involvement of free radicals in the MH syndrome.

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