[Effects of halothane, caffeine and ryanodine on the intracellular calcium store in blood mononuclear cells].
To evaluate the possibility of using blood cells in the screening test for susceptibility to malignant hyperthermia (MH), we examined the effect of halothane and caffeine on cytoplasmic free calcium concentration ([Ca]i) in mononuclear cells. Blood mononuclear cells were isolated from guinea pigs or normal human volunteers, loaded with fura-2 AM and changes in the calcium signal (340nm/380nm ratio) after the application of halothane and/or caffeine were measured. Halothane above 5 mM caused a large increase in [Ca]i, but this increase was mostly abolished by the removal of extra-cellular calcium using EGTA. On the other hand, caffeine caused no observable change in the calcium signal. Pre-treatment with ryanodine did not change the calcium signal brought about by halothane or ionomycin. We conclude from this study that there is no calcium-induced calcium release (CICR) mechanism detectable by this method in blood mononuclear cells. As we consider that the main cause of the typical MH is the abnormality in the CICR mechanism, it seems difficult to screen MH susceptibility by using blood mononuclear cells. Further studies will be necessary using MH susceptible swines or patients.
Kawana
Y
Y
Department of Pharmacology, Faculty of Medicine, University of Tokyo.
Iino
M
M
Oyamada
H
H
Endo
M
M
D000818:Animals; D002110:Caffeine; D002118:Calcium / Q000097:blood*; D004198:Disease Susceptibility; D006221:Halothane; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000378:metabolism; D008305:Malignant Hyperthermia / Q000503:physiopathology*; D008954:Models, Biological; D012433:Ryanodine
D012433:Ryanodine; D002110:Caffeine; D002118:Calcium; D006221:Halothane