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Titolo:
SODIUM-CHANNEL IN HUMAN-MALIGNANT HYPERTHERMIA
Autore:
FLETCHER JE; WIELAND SJ; KARAN SM; BEECH J; ROSENBERG H;
Indirizzi:
ALLEGHENY UNIV HLTH SCI,DEPT ANESTHESIOL MS310,BROAD & VINE ST PHILADELPHIA PA 19102 UNIV PENN,NEW BOLTON CTR,SCH VET MED,DEPT CLIN STUDIES KENNETT SQ PA 19348 UNIFORMED SERV UNIV HLTH SCI,DEPT ANESTHESIOL BETHESDA MD 20814 ALLEGHENY UNIV HLTH SCI,DEPT ANAT & NEUROBIOL PHILADELPHIA PA 19102
Titolo Testata:
Anesthesiology
fascicolo: 5, volume: 86, anno: 1997,
pagine: 1023 - 1032
SICI:
0003-3022(1997)86:5<1023:SIHH>2.0.ZU;2-M
Fonte:
ISI
Lingua:
ENG
Soggetto:
HUMAN SKELETAL-MUSCLE; RYANODINE RECEPTOR; CONTRACTURE TEST; NORTH-AMERICAN; HALOTHANE; CAFFEINE; SUSCEPTIBILITY; TETRODOTOXIN; MEMBRANE; SWINE;
Keywords:
ANESTHETICS, VOLATILE; HYPERTHERMIA, MALIGNANT; RIGIDITY, MUSCLE; SODIUM CHANNEL; SUCCINYLCHOLINE;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
47
Recensione:
Indirizzi per estratti:
Citazione:
J.E. Fletcher et al., "SODIUM-CHANNEL IN HUMAN-MALIGNANT HYPERTHERMIA", Anesthesiology, 86(5), 1997, pp. 1023-1032

Abstract

Background: The abundance of a specific sodium channel subunit (SkM2)appeared to be altered in vitro in cell cultures from persons susceptible to malignant hyperthermia. This study sought to determine whetherthese findings are artifacts of cell culture or whether they may be relevant to malignant hyperthermia. Methods: Regulation of transcript levels of SkM2, a specific sodium channel cu-subunit, was determined bymRNA analysis. Functional SkM2 protein was estimated in biopsy sections of vastus lateralis muscle by inhibiting the directly elicited muscle twitch by tetrodotoxin, which can differentiate at least three sodium currents in skeletal muscle. Results: The transcript levels of SkM2were depressed by 115-fold in six of seven persons susceptible to malignant hyperthermia; and the functional expression of the SkM2 protein, based on the tetrodotoxin sensitivity of the directly elicited twitch, was decreased by at least fourfold in muscle from persons susceptible to malignant hyperthermia compared with persons who were not susceptible. Conclusions: As in previous studies in cell culture, altered mRNA and/or the functional expression of a specific subunit of the sodium channel (SkM2) was found in biopsy sections of muscle from all 12 persons examined who were susceptible to malignant hyperthermia but in none of the 16 nonsusceptible participants. Human malignant hyperthermia is a heterogeneous disorder, and the down-regulation of SkM2 may be involved in the final common pathway through which mutations in any one of several proteins, including the ryanodine receptor, could render a person susceptible.

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Documento generato il 23/01/20 alle ore 12:27:53