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 language | English |
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Pages (from-to) | 435-442 |
Number of pages | 8 |
Journal | Free Radical Biology and Medicine |
Volume | 14 |
Issue number | 4 |
DOIs | |
Publication status | Published - 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