Permeabilisation of the sarcolemma in mouse diaphragm exposed to Bay K 8644 in vitro: time course, dependence on Ca2+ and effects of enzyme inhibitors

Permeabilisation of the sarcolemma in mouse diaphragm exposed to Bay K 8644 in vitro: time course, dependence on Ca2+ and effects of enzyme inhibitors
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体外暴露于 Bay K 8644 的小鼠膈肌肌膜的透化:时间进程、对 Ca2 的依赖性以及酶抑制剂的作用

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发表时间:
2004
影响因子:
12.7
通讯作者:
S. Publicover
S. Publicover
中科院分区:
医学1区
文献类型:
--
作者:
J. Howl;S. Publicover

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总结在体外用Ca 2+通道激动剂Bay K 8644(1 μM)处理部分去极化的小鼠膈肌,可诱导肌膜的透化(通过普罗西翁黄的渗透可见)。处理2小时后,Procion黄染色广泛(74%的纤维),但60分钟后可忽略不计,此时肌纤维分解进展良好,[Ca 2 +]i升高最小(Howl和Publicover 1989)。在无Ca 2+的盐水中,透化被抑制,并且在极化纤维中不太明显。自由基生成的抑制剂(特别是OH-)提供了相当大的保护,对海湾K 8644诱导的膜透化的肌膜。磷脂酶A2和脂氧合酶的抑制也是有效的,但黄嘌呤氧化酶(别嘌呤醇)的抑制作用很小。可以得出结论,湾K 8644治疗的初始效果是增加Ca 2+内流通过Ca 2+通道在肌膜,这一行动随后诱导膜透化。膜损伤可能是由于自由基的产生和磷脂酶A2的激活而发生的,两者都是由[Ca+]i升高引起的。
SummaryTreatment of partially depolarised mouse diaphragm muscle in vitro with the Ca2+-channel agonist Bay K 8644 (1 μM) induces permeabilisation of the sarcolemma (visualised by penetration of procion yellow). Procion yellow staining was widespread (74% of fibres) after 2 h of treatment, but was negligible after 60 min, a time at which myofibre breakdown is well advanced and elevation of [Ca2+]i is minimal (Howl and Publicover 1989). Permeabilisation was inhibited in Ca2+-free saline, and was much less pronounced in polarised fibres. Inhibitors of free radical generation (particularly OH⊙) afforded considerable protection to the muscle membrane against Bay K 8644-induced membrane permeabilisation. Inhibition of phospholipase A2 and lipoxygenase were also effective, but inhibition of xanthine oxidase (by allopurinol) had little effect. It is concluded that the initial effect of Bay K 8644 treatment is to increase Ca2+ influx through Ca2+ channels at the sarcolemma, and that this action subsequently induces membrane permeabilisation. Membrane damage probably occurs due to free radical generation and activation of phospholipase A2, both resulting from elevation of [Ca+]i.
疾病生物学:凝固性坏死发病机制中的膜损伤和钙稳态。
DOI: --
发表时间: 1982
期刊: Laboratory investigation; a journal of technical methods and pathology
影响因子: --
作者:
Farber,JL
通讯作者: Farber,JL