红氧依赖Cd2+抑制BK型Ca2+激活的K+通道
Guohui Zhang1, Huanghe Yang2, Yuyin Wang1
1Department of Biomedical Engineering, Washington University, St. Louis, Missouri.
Biophysical journal
|February 24, 2024
概括
像DTT这样的降解剂抑制了激活的大导率Ca2+激活K+ (BK) 通道. 这种由氧化剂逆转的抑制表明了氧化还原调节机制,但BK通道中的氨酸突变不会影响这种效应.
科学领域:
- 离子通道生理学 离子通道生理学
- 分子生物物理学的分子生物物理学.
- 细胞电生理学 细胞电生理学
背景情况:
- 由Slo1子单元形成的大导电性Ca2+激活K+通道 (BK通道),由细胞内Ca2+和其他双价 (如Cd2+) 激活.
- Cd2+通过将导电电压关系转移到更负的电位来激活BK通道.
研究的目的:
- 研究降解剂对Cd2+抑制BK通道的影响.
- 探索底层的氧化还原机制,并确定参与这种调节的分子组件.
主要方法:
- 利用内外补丁电生理学来记录BK通道电流.
- 应用了还原剂 (二甲二醇,DTT) 和氧化剂 (H2O2) 来研究氧化还原调节.
- 检查了BK通道突变,包括Core-MT (细胞质域删除),以及其他K+通道类型 (Slo3,Shaker).
- 通过在Slo1子单元中突变它们来研究氨酸残留的作用.
主要成果:
- 含有BK通道的内外补丁的二二甲醇 (DTT) 处理导致了Cd2+诱导电流的完全抑制.
- 这种DTT-依赖的Cd2+抑制在用H2O2治疗后是可逆的,这表明有氧还原调节.
- 在Core-MT突变BK通道和质子激活Slo3通道中观察到类似的抑制,但在Shaker K+通道中没有.
- 令人惊的是,Slo1亚单元中所有氨酸残留物的突变没有影响DTT依赖的Cd2+抑制.
结论:
- 一个氧化还原反应似乎调节了BK通道的Cd2+抑制,这种抑制是由像DTT这样的降解剂调节的.
- 该机制可能涉及与Cd2+协调的醇组,但Slo1中氨酸突变缺乏效果存在悖论.
- 需要进一步调查,以解决显然的逆转氧化调节和Slo1.1中未涉及已识别的氨酸残留物之间的矛盾.
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