AJP - Cell Physiology, Vol 258, Issue 3 C495-C503, Copyright © 1990 by American Physiological Society
Halothane-dependent release of intracellular Ca2+ in blood cells in malignant hyperthermia
A. Klip, G. B. Mills, B. A. Britt and M. E. Elliott
Department of Cell Biology, Hospital for Sick Children, Toronto, Ontario, Canada.
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)
