ISSN:
1432-2013
Keywords:
Ca2+ microelectrodes cADP-ribose Calcium Dantrolene Heparin Malignant hyperthermia Ruthenium red Ryanodine Skeletal muscle
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. Cyclic adenosine diphosphate-ribose (cADPR) is an endogenous metabolite of β-NAD+ that induces Ca2+ release from intracellular stores in many tissues. Microinjection of cADPR (0.5 or 1 µM) increased the intracellular resting Ca2+ concentration ([Ca2+]i) in intact swine skeletal muscle in a dose-dependent manner. However, the increase in [Ca2+]i was greater in malignant-hyperthermia-susceptible (MHS) fibers than in non-susceptible (MHN) fibers. Incubation of muscle fibers in low external Ca2+ solution or in the presence of L-type Ca2+ channel entry blockers, or intracellular microinjection of heparin or ruthenium red did not modify the effect of cADPR on [Ca2+]i. Dantrolene (50 µM), a known inhibitor of intracellular Ca2+ release, decreased resting [Ca2+]i and prevented the cADPR-induced increase in [Ca2+]i. These results provide evidence: (1) for the existence of Ca2+ release mechanisms occurring via non-ryanodine or inositol 1,4,5-trisphosphate (InsP 3) receptor mechanisms; (2) that MHS skeletal muscles exhibit a higher responsiveness to cADP-ribose-induced release of Ca2+ and (3) that the ability of dantrolene to block cADP-ribose-induced release of Ca2+ could be related to its pharmacologic effect on resting [Ca2+]i.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/s004240000291
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