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 Ca2+ concentration ([Ca2+]i) using double-barreled, Ca2+-selective microelectrodes in myoballs prepared from skeletal muscle of MH-susceptible (MHS) and MH-nonsusceptible (MHN) swine. Resting [Ca2+]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 [Ca2+]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 [Ca2+]i, raised the concentration of caffeine and 4-CmC required to cause an elevation of [Ca 2+]i, and reduced the amount of Ca2+ 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 [Ca2+]i levels in these cells.
| Original language | English (US) |
|---|---|
| Journal | American Journal of Physiology - Cell Physiology |
| Volume | 288 |
| Issue number | 3 57-3 |
| DOIs | |
| State | Published - Mar 2005 |
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Keywords
- 1,2-bis(2-aminophenoxy)ethane-N,N,N′,N′- tetraacetic acid
- Calcium homeostasis
ASJC Scopus subject areas
- Clinical Biochemistry
- Cell Biology
- Physiology
Cite this
Enhanced response to caffeine and 4-chloro-m-cresol in malignant hyperthermia-susceptible muscle is related in part to chronically elevated resting [Ca2+]i . / López, José R.; Linares, Nancy; Pessah, Isaac N; Allen, Paul D.
In: American Journal of Physiology - Cell Physiology, Vol. 288, No. 3 57-3, 03.2005.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Enhanced response to caffeine and 4-chloro-m-cresol in malignant hyperthermia-susceptible muscle is related in part to chronically elevated resting [Ca2+]i
AU - López, José R.
AU - Linares, Nancy
AU - Pessah, Isaac N
AU - Allen, Paul D.
PY - 2005/3
Y1 - 2005/3
N2 - 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 Ca2+ concentration ([Ca2+]i) using double-barreled, Ca2+-selective microelectrodes in myoballs prepared from skeletal muscle of MH-susceptible (MHS) and MH-nonsusceptible (MHN) swine. Resting [Ca2+]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 [Ca2+]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 [Ca2+]i, raised the concentration of caffeine and 4-CmC required to cause an elevation of [Ca 2+]i, and reduced the amount of Ca2+ 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 [Ca2+]i levels in these cells.
AB - 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 Ca2+ concentration ([Ca2+]i) using double-barreled, Ca2+-selective microelectrodes in myoballs prepared from skeletal muscle of MH-susceptible (MHS) and MH-nonsusceptible (MHN) swine. Resting [Ca2+]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 [Ca2+]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 [Ca2+]i, raised the concentration of caffeine and 4-CmC required to cause an elevation of [Ca 2+]i, and reduced the amount of Ca2+ 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 [Ca2+]i levels in these cells.
KW - 1,2-bis(2-aminophenoxy)ethane-N,N,N′,N′- tetraacetic acid
KW - Calcium homeostasis
UR - http://www.scopus.com/inward/record.url?scp=13644264675&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=13644264675&partnerID=8YFLogxK
U2 - 10.1152/ajpcell.00297.2004
DO - 10.1152/ajpcell.00297.2004
M3 - Article
C2 - 15537710
AN - SCOPUS:13644264675
VL - 288
JO - American Journal of Physiology - Renal Fluid and Electrolyte Physiology
JF - American Journal of Physiology - Renal Fluid and Electrolyte Physiology
SN - 1931-857X
IS - 3 57-3
ER -