Enhanced Ca2+-induced calcium release by isolated sarcoplasmic reticulum vesicles from malignant hyperthermia susceptible pig muscle.
Enhanced Ca2+-induced calcium release by isolated sarcoplasmic reticulum vesicles from malignant hyperthermia susceptible pig muscle.
复制标题
从恶性高热易感猪肌肉中分离出的肌浆网囊泡增强了 Ca2 诱导的钙释放。
DOI:
10.1016/0005-2736(86)90234-8
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发表时间:
1986
期刊:
影响因子:
--
通讯作者:
Louis,CF
中科院分区:
文献类型:
--
作者:
Mickelson,JR;Ross,JA;Reed,BK;Louis,CF
To further define the possible involvement of sarcoplasmic reticulum calcium accumulation and release in the skeletal muscle disorder malignant hyperthermia (MH), we have examined various properties of sarcoplasmic reticulum fractions isolated from normal and MH-susceptible pig muscle. A sarcoplasmic reticulum preparation enriched in vesicles derived from the terminal cisternae, was further fractionated on discontinuous sucrose density gradients (Meissner, G.(1984) J. Biol. Chem. 259, 2365–2374). The resultant MH-susceptible and normal sarcoplasmic reticulum fractions, designated F 0 F 4, did not differ in yield, cholesterol and phospholipid content, or nitrendipine binding capacity. Calcium accumulation (0.27 μmol Ca/mg per min at 22° C), Ca 2+-ATPase activity (0.98 μmol P i/mg per min at 22° C), and calsequestrin content were also similar for MH-susceptible and normal sarcoplasmic reticulum fraction F 3. To examine sarcoplasmic reticulum calcium release, fraction F 3 vesicles were passively loaded with 45 Ca (approx. 40 nmol Ca/mg), and rapidly diluted into a medium of defined Ca 2+ concentration. Upon dilution into 1 μM Ca 2+, the extent of Ca 2+-dependent calcium release measured after 5 s was significantly greater for MH-susceptible than for normal sarcoplasmic reticulum, 65.9±2.8% vs. 47.7±3.9% of the loaded calcium, respectively. The C 1 2 for Ca 2+ stimulation of this calcium release (5 s value) from MH-susceptible sarcoplasmic reticulum also appeared to be shifted towards a higher Ca 2+-sensitivity when compared to normal sarcoplasmic reticulum. Dantrolene had no effect on calcium release from fraction F 3, however, halothane (0.1–0.5 mM) increased the extent of calcium release (5 s) similarly in both MH-susceptible and normal sarcoplasmic reticulum. Furthermore, Mg 2+ was less effective at inhibiting, while ATP and caffeine were more effective in stimulating, this Ca 2+-dependent release of calcium from MH-susceptible, when compared to normal sarcoplasmic reticulum. Our results demonstrate that while sarcoplasmic reticulum calcium-accumulation appears unaffected in MH, aspect (s) of the sarcoplasmic reticulum Ca 2+-induced calcium release mechanism are altered. Although the role of the Ca 2+-induced calcium release mechanism of sarcoplasmic reticulum in situ is not yet clear, our results suggest that an abnormality in the regulation of sarcoplasmic reticulum calcium release may play an important role in the MH syndrome.
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DOI:
--
发表时间:
1984
期刊:
The Journal of biological chemistry
影响因子:
--
作者:
Ikemoto,N;Antoniu,B;Kim,DH
通讯作者:
Kim,DH
影响因子:
5
作者:
G. Gronert;J. Heffron;S. R. Taylor
通讯作者:
S. R. Taylor
影响因子:
9.8
作者:
H. Isaacs;J. Heffron
通讯作者:
J. Heffron
影响因子:
4.1
作者:
K. S. Cheah;A. Cheah
通讯作者:
A. Cheah
影响因子:
3.4
作者:
DOWNER, NW
通讯作者:
DOWNER, NW