ISSN:
1432-1912
Keywords:
Inositol 1,4,5-trisphosphate
;
Malignant hyperthermia
;
Calcium
;
Skeletal muscle
;
Dantrolene
;
Ca2+ microelectrode
;
Nitrendipine
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
Abstract Malignant hyperthermia (MH) is associated with abnormal regulation of intracellular calcium in skeletal muscle fibers. Besides a mutation in the ryanodine receptor gene, an increase in inositol, 1,4,5-trisphosphate (InsP3) levels could be a possible candidate for the abnormal regulation of intracellular calcium. However, the effect of InsP3 on [Ca2+]i in MH is not known. Microinjection of InsP3 increased intracellular Ca2+ in intact skeletal muscle from malignant hyperthermia susceptible swines (MHS) with a higher potency and efficacy than in muscles from nonsusceptible (MHN) swines. Omission of extracellular Ca2+ or incubation of muscle fibers with Ca2+ channel blockers did not modify the response to InsP3. However, dantrolene (50 μM) a known blocker of intracellular Ca2+ release, decreased resting intracellular Ca2+ concentration and prevented the InsP3-induced increase in intracellular Ca2+. This suggests (i) that MHS skeletal muscles exhibit a higher responsiveness to InsP3-induced release of Ca2+, which could implicate InsP3 in the pathophysiology of MH, and (ii) that the beneficial effect of dantrolene in MHS could be related to its ability to prevent the InsP3-induced release of Ca2+.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/BF00172783
Permalink