阿米奥达龙对心脏延迟整流器K(+) 电流的两个组件的短期和长期影响
K Kamiya1, A Nishiyama, K Yasui
1Department of Circulation, Research Institute of Environmental Medicine, Nagoya University, Nagoya, Japan. kamiya@riem.nagoya-u.ac.jp
Circulation
|March 10, 2001
概括
阿米奥达龙对心脏离子通道的影响因治疗时间而异. 短期使用会抑制I(Kr),而长期使用会降低I(Ks),影响着动脉节律失常治疗.
科学领域:
- 心脏病学 心脏病学
- 药理学 药理学是指药理学的学科.
- 分子生物学分子生物学
背景情况:
- 阿米奥达龙对于治疗结构性心脏病患者的危及生命的动脉节律失调至关重要.
- 它对心脏离子通道的复杂影响可能会因短期和长期管理而有所不同.
研究的目的:
- 调查阿米奥达龙在短期和长期服用后对延迟整流器电流 (I(K)) I(Ks) 和I(Kr) 的两个组成部分的差异作用.
- 为了比较阿米奥达龙对原生子心脏通道和克隆人类心脏通道的影响.
主要方法:
- 在子心室肌细胞上使用全细胞电压技术来测量I ((K),I ((Kr) 和I ((Ks)).
- 使用的特定阻断剂 (I(Ks的Chromanol 293B,I(Kr的E-4031).
- 在克隆HERG (I(Kr)) 和KvLQT1/minK (I(Ks)) 通道表达的Xenopus卵细胞中评估了效应.
- 对子进行4周的口服阿米奥达龙,以研究长期影响.
主要成果:
- 在子肌细胞中,短期阿米奥达龙抑制了I(Kr) (IC50=2.8μmol/L),对I(Ks的影响很小.
- 在卵细胞中,阿米奥达龙抑制了HERG (I(Kr)) 电流 (IC50=38 μmol/L),但不是KvLQT1/minK (I(Ks)) 电流.
- 长期的阿米奥达龙治疗 (4周) 减少了总I(K) 的55%,并改变了I(Kr) /I(Ks) 的比率.
- 在长期治疗阿米奥达龙后,ERG,KVLQT1或minK的mRNA水平没有显著变化.
结论:
- 阿米奥达龙对I(Kr) 和I(Ks) 产生不同的影响,这取决于服用时间.
- 短期阿米奥达龙主要向并抑制I(Kr).
- 长期使用阿米奥达龙会导致I(Ks) 的降低.
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