Halothane-dependent release of intracellular Ca2+ in blood cells in malignant hyperthermia.
The concentration of ionized cytosolic calcium [( Ca2+]i) was determined in peripheral blood mononuclear cells from normal and malignant hyperthermia (MH)-susceptible humans and pigs, using the fluorescent Ca2+ indicator indo-1. [Ca2+]i was slightly but significantly elevated in cells from MH human cells relative to normal cells (198 +/- 18 nM, n = 15, and 146 +/- 14 nM, n = 11, respectively, P less than 0.05). Anesthetic concentrations of halothane in the cell suspension resulted in a rapid increase in [Ca2+]i in cells from both normal and MH humans or pigs. The increases (delta) were more pronounced in cells from MH subjects than from normal individuals (delta at 5.7 mM halothane: 245 +/- 53 vs. 57 +/- 11 nM, respectively) and from MH than from normal pigs (delta of 241 +/- 63 vs. 53 +/- 27 nM, respectively). Removal of extracellular Ca2+ obliterated the delta[Ca2+]i caused by halothane in cells from normal humans or pigs but only decreased by about half the delta[Ca2+]i in cells from MH humans or pigs. In 1,2-bis-(aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA)-loaded cells, in the absence of extracellular Ca2+, halothane failed to increase [Ca2+]i. This suggests that buffering Cai2+ with BAPTA precludes detection of release of Ca2+ from intracellular stores, explaining the previous observations made with quin2, a highly chelating Ca2+ indicator. It is concluded that clinical concentrations of halothane allow influx of Ca2+ in cells from both normal and MH-susceptible individuals but release Ca2+ from intracellular stores selectively in cells from the latter group.(ABSTRACT TRUNCATED AT 250 WORDS)
Klip
A
A
Department of Cell Biology, Hospital for Sick Children, Toronto, Ontario, Canada.
Mills
G B
GB
Britt
B A
BA
Elliott
M E
ME
D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000097:blood*; D003600:Cytosol / Q000378:metabolism; D004198:Disease Susceptibility; D004533:Egtazic Acid / Q000494:pharmacology / Q000031:analogs & derivatives; D006221:Halothane / Q000494:pharmacology*; D006801:Humans; D008305:Malignant Hyperthermia / Q000503:physiopathology* / Q000662:veterinary; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism*; D009119:Muscle Contraction / Q000187:drug effects*; D009132:Muscles / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology; D013552:Swine; D013553:Swine Diseases / Q000503:physiopathology
D002110:Caffeine; D004533:Egtazic Acid; C025603:1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid; D002118:Calcium; D006221:Halothane