Oxidative regulation of large conductance calcium-activated potassium channels.
Oxidative regulation of large conductance calcium-activated potassium channels.
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DOI：
10.1085/jgp.117.3.253
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发表时间：
2001-03
影响因子：
3.8
通讯作者：
Hoshi, T
中科院分区：
文献类型：
--
作者：
Tang, XD;Daggett, H;Hanner, M;Garcia, ML;McManus, OB;Brot, N;Weissbach, H;Heinemann, SH;Hoshi, T
活性氧/氮在体内很容易产生，通过氧化修饰各种蛋白质在许多生理和病理条件下发挥作用，如阿尔茨海默病和帕金森病。先前的研究表明，大电导Ca2+激活的K+通道（BKCa或Slo）受氧化还原调节。然而，氧化是否增加或减少通道活性存在矛盾的结果。我们使用优先氧化蛋氨酸的氯胺- t来研究蛋氨酸氧化在哺乳动物细胞中表达的克隆人类Slo （hSlo）通道中的功能后果。在Ca2+缺乏的情况下，氧化剂将稳态宏观电导率向更负的方向移动，并减缓了失活。得到的结果表明，氧化增强了特定的电压依赖的打开转变，减缓了限速的关闭转变。hSlo活性的增强被酶肽蛋氨酸亚砜还原酶部分逆转，表明这种上调是由蛋氨酸氧化介导的。相比之下，过氧化氢和半胱氨酸特异性试剂DTNB、MTSEA和PCMB降低了通道活性。氯胺- t与K+通道阻滞剂TEA同时施用时效果要差得多，这与目标蛋氨酸位于通道孔内的可能性是一致的。蛋氨酸氧化对Slo通道的调节可能是细胞电兴奋性和代谢之间的重要联系。
Reactive oxygen/nitrogen species are readily generated in vivo, playing roles in many physiological and pathological conditions, such as Alzheimer's disease and Parkinson's disease, by oxidatively modifying various proteins. Previous studies indicate that large conductance Ca2+-activated K+ channels (BKCa or Slo) are subject to redox regulation. However, conflicting results exist whether oxidation increases or decreases the channel activity. We used chloramine-T, which preferentially oxidizes methionine, to examine the functional consequences of methionine oxidation in the cloned human Slo (hSlo) channel expressed in mammalian cells. In the virtual absence of Ca2+, the oxidant shifted the steady-state macroscopic conductance to a more negative direction and slowed deactivation. The results obtained suggest that oxidation enhances specific voltage-dependent opening transitions and slows the rate-limiting closing transition. Enhancement of the hSlo activity was partially reversed by the enzyme peptide methionine sulfoxide reductase, suggesting that the upregulation is mediated by methionine oxidation. In contrast, hydrogen peroxide and cysteine-specific reagents, DTNB, MTSEA, and PCMB, decreased the channel activity. Chloramine-T was much less effective when concurrently applied with the K+ channel blocker TEA, which is consistent with the possibility that the target methionine lies within the channel pore. Regulation of the Slo channel by methionine oxidation may represent an important link between cellular electrical excitability and metabolism.
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DOI：
10.1085/jgp.109.5.647
发表时间：
1997-05
期刊：
The Journal of general physiology
影响因子：
--
作者：
Cui J;Cox DH;Aldrich RW
通讯作者：
Aldrich RW
影响因子：
5.5
作者：
Ahern, GP;Hsu, SF;Jackson, MB
通讯作者：
Jackson, MB
影响因子：
3.4
作者：
DURELL, SR;GUY, HR
通讯作者：
GUY, HR
影响因子：
3.5
作者：
BECKSPEIER, I;LEUSCHEL, L;MAIER, KL
通讯作者：
MAIER, KL
DOI：
10.1152/ajpheart.2000.278.6.h1883
发表时间：
2000-06-01
影响因子：
4.8
作者：
Brzezinska, AK;Gebremedhin, D;Elliott, SJ
通讯作者：
Elliott, SJ