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)

Succinylcholine (Sch) which is a cholinergic neuromuscular blocker has been known to occasionally lead to episodes of malignant hyperthermia in swine and humans. In order to find whether it produces any hyperthermic effects through action on medial preoptic area, experiments were carried on by administering intracerebrally the chemical into the medial preoptic area through an in-dwelling cannula-cum-electrode in the free moving rat. The changes in body temperature and the local EEG were studied. For comparison purpose, the effects of carbachol, atropine and phenylephrine were also studied. Further, in the curarized state of no muscular activity, the effect of SCh on the preoptic area was again tested and also the changes in the other autonomic parameters of heart rate and galvanic skin resistance (GSR) were studied. It was observed that SCh given into preoptic area caused a clear hyperthermic effect. The effect was countered by prior administration of atropine into the site. After SCh the local EEG changed into a high amplitude slow wave format. The heart rate was not altered but the GSR increased by two-fold. Carbachol caused a rise in body temperature, heart rate and also GSR. SCh also caused a reduction in noradrenaline content of the hypothalamus by 23% while no change in dopamine and serotonin occurred. Serotonin increased by 28% in the brainstem with no change in the other amines. Septum showed an increase of noradrenaline and dopamine contents by 40% and 25% respectively. Keeping in view the monoaminergic connections and thermoregulatory role of the preoptic area, one may postulate that SCh could inhibit the warm sensors and the controls of the dual sympathetic mechanism which normally leads to an increase of sudomotor activity and a decrease of vasomotor activity, the inhibition resulting in rise of body temperature.
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PMID:Effects of succinylcholine and related substances administered into the medial preoptic area on the local EEG, body temperature, heart rate, galvanic skin resistance and biogenic amines. 384 71

The mechanism of action of volatile anesthetics is not completely understood. Calcium release from internal stores may alter signaling pathways that influence neurotransmission. Abnormalities of the regulation of intracellular calcium concentration ([Ca2+]i) from patients with malignant hyperthermia is a hallmark of this syndrome indicating the potential of these agents to interact with proteins involved in Ca2+ signaling. In the present study, a cholinergic cell line (SN56) was used to examine whether the release of calcium from intracellular stores occurs in the presence of sevoflurane. Changes in [Ca2+]i were measured using fluo-4, a fluorescent calcium sensitive dye and laser scanning confocal microscopy. Sevoflurane induced an increase on [Ca2+]i from SN56 cells. The sevoflurane-induced increase on [Ca2+]i remained even when the cells were perfused with medium lacking extracellular calcium. However, this effect was abolished by BAPTA-AM, a chelator of intracellular calcium, suggesting the involvement of intracellular Ca2+ stores. Using cyclopiazonic acid, an inhibitor of sarcoplasmic/endoplasmic reticulum Ca(2+)-ATPase, we investigated whether the depletion of intracellular Ca2+ stores interfered with the effect of sevoflurane. In the presence of this agent, sevoflurane caused a small but not significant rise on [Ca2+]i of the SN56 cells. Dantrolene, an inhibitor of ryanodine-sensitive calcium stores did not modify the sevoflurane increase on [Ca2+]i. Carbachol, a drug that releases Ca2+ from the IP3 pool, abolished the effect of sevoflurane. In addition, xestospongin D, a cell-permeant IP3 receptor antagonist, decreased significantly the sevoflurane increase on [Ca2+]i. Our data suggest that the sevoflurane-induced increase on [Ca2+]i from SN56 cells occurs through the release of calcium from IP3-sensitive calcium stores.
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PMID:The effect of sevoflurane on intracellular calcium concentration from cholinergic cells. 1653 63