Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024591 (malignant hyperthermia)
 2,353 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The purpose of these experiments was to determine if the Ca2+ agonist BAY K 8644 and the Ca2+ antagonist nifedipine alter the mechanical responses of malignant hyperthermia-susceptible (MHS) skeletal muscle to halothane and caffeine. Muscle fiber bundles were dissected from MHS porcine skeletal muscle and exposed to BAY K 8644 (10 microM), nifedipine (1 microM), low-Ca2+ media [Ca2+ replaced by 1 mM ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid], or diltiazem (30 microM) administered alone and with halothane (3%) or caffeine (0.5-0.8 mM). When administered alone, both halothane and BAY K 8644 evoked a significant change in resting tension (i.e., contracture) of 193.7 +/- 61.0 and 51.9 +/- 21.5 mN/cm2, respectively. When administered in combination, BAY K 8644 had no effect on the magnitude of the halothane contracture (195.2 +/- 58.6 mN/cm2) but reduced its onset time from 306.7 +/- 36.3 to 105.9 +/- 8.9 s. Nifedipine, low Ca2+, and diltiazem significantly reduced the halothane contracture (103.1 +/- 30.3, 123.1 +/- 20.6, and 112.6 +/- 16.2 mN/cm2, respectively) but had no effect on its onset time. In addition, low Ca2+ reduced the magnitude of the BAY K 8644 contracture (8.2 +/- 2.1 mN/cm2). BAY K 8644 also increased contractures induced by low caffeine concentrations (0.5-2.0 mM) but did not alter contractures induced by 4.0 and 8.0 mM caffeine, whereas nifedipine, low Ca2+, and diltiazem had no effect on these contractures. These results suggest that extracellular Ca2+ influx may have some influence on halothane but not on caffeine contractures of MHS skeletal muscle.
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PMID:BAY K 8644 and nifedipine alter halothane but not caffeine contractures of malignant hyperthermic muscle fibers. 171 70

We have investigated in malignant hyperthermia susceptible swine in vivo the effects on halothane initiation of the MH syndrome and on the established syndrome of five calcium channel blocking drugs--nifedipine, nisoldipine, diltiazem, verapamil and flunarazine. Nifedipine alone caused attenuation of halothane-initiated malignant hyperthermia to the extent of blocking onset of the syndrome in 29% of animals for the 60 minute period of exposure. In the face of the established malignant hyperthermia syndrome, all the drugs tested were therapeutically completely ineffective.
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PMID:The effects of calcium channel blocking drugs on halothane initiation of malignant hyperthermia in MHS swine and on the established syndrome. 339 13

Myotubes expressing wild type RyR1 (WT) or RyR1 with one of three malignant hyperthermia mutations R615C, R2163C, and T4826I (MH) were exposed sequentially to 60 mm KCl in Ca(2+)-replete and Ca(2+)-free external buffers (Ca+ and Ca-, respectively) with 3 min of rest between exposures. Although the maximal peak amplitude of the Ca(2+) transients during K(+) depolarization was similar for WT and MH in both external buffers, the rate of decay of the sustained phase of the transient during K(+) depolarization (decay rate) in Ca+ was 50% slower for MH. This difference was eliminated in Ca-, and the relative decay rates were faster for both genotypes than in Ca+. The integrated Ca(2+) transient in Ca-compared with Ca+ was reduced by 50-60% for MH and 20% for WT. The decay rate was not affected by [K(+)] x [Cl(-)] product or NiCl(2) (2 mm) supplementation of Ca-. The addition of La(2+) (0.1 mm), or SKF 96365 (20 microm) to Ca+ significantly accelerated decay rates for both WT and MH, but their effect was significantly greater in MH. Nifedipine (1 microm) had no effect, suggesting that the mechanism for this difference was not a reduction in L-type Ca(2+) channel Ca(2+) current. These data strongly suggest: 1) the decay rate in skeletal myotubes is related in part to Ca(2+) entry through the ECCE channel; 2) the MH mutations enhance ECCE compared with wild type; and 3) the increased Ca(2+) entry might play a significant role in the pathophysiology of MH.
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PMID:Enhanced excitation-coupled calcium entry in myotubes is associated with expression of RyR1 malignant hyperthermia mutations. 1794 9