Enhanced response to caffeine and 4-chloro-m-cresol in malignant hyperthermia-susceptible muscle is related in part to chronically elevated resting [Ca2+]i.
Am J Physiol Cell Physiol
; 288(3): C606-12, 2005 Mar.
Article
em En
| MEDLINE
| ID: mdl-15537710
ABSTRACT
Malignant hyperthermia (MH) is a potentially fatal pharmacogenetic syndrome caused by exposure to halogenated volatile anesthetics and/or depolarizing muscle relaxants. We have measured intracellular Ca(2+) concentration ([Ca(2+)](i)) using double-barreled, Ca(2+)-selective microelectrodes in myoballs prepared from skeletal muscle of MH-susceptible (MHS) and MH-nonsusceptible (MHN) swine. Resting [Ca(2+)](i) was approximately twofold in MHS compared with MHN quiescent myoballs (232 +/- 35 vs. 112 +/- 11 nM). Treatment of myoballs with caffeine or 4-chloro-m-cresol (4-CmC) produced an elevation in [Ca(2+)](i) in both groups; however, the concentration required to cause a rise in [Ca(2+)](i) elevation was four times lower in MHS than in MHN skeletal muscle cells. Incubation of MHS cells with the fast-complexing Ca(2+) buffer BAPTA reduced [Ca(2+)](i), raised the concentration of caffeine and 4-CmC required to cause an elevation of [Ca(2+)](i), and reduced the amount of Ca(2+) release associated with exposure to any given concentration of caffeine or 4-CmC to MHN levels. These results suggest that the differences in the response of MHS skeletal myoballs to caffeine and 4-CmC may be mediated at least in part by the chronic high resting [Ca(2+)](i) levels in these cells.
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Base de dados:
MEDLINE
Assunto principal:
Cafeína
/
Cálcio
/
Ácido Egtázico
/
Músculo Esquelético
/
Cresóis
/
Hipertermia Maligna
Limite:
Animals
Idioma:
En
Ano de publicação:
2005
Tipo de documento:
Article