An electrostatic potassium channel opener targeting the final voltage sensor transition

被引:60
作者
Borjesson, Sara I. [1 ]
Elinder, Fredrik [1 ]
机构
[1] Linkoping Univ, Div Cell Biol, Dept Clin & Expt Med, SE-58185 Linkoping, Sweden
基金
瑞典研究理事会;
关键词
GATED ION CHANNELS; POLYUNSATURATED FATTY-ACIDS; SHAKER K+ CHANNEL; GATING-MODIFIER; SODIUM-CHANNEL; RECEPTOR-SITE; PORE DOMAIN; TARANTULA TOXINS; KETOGENIC DIET; BINDING-SITE;
D O I
10.1085/jgp.201110599
中图分类号
Q4 [生理学];
学科分类号
071003 ;
摘要
Free polyunsaturated fatty acids (PUFAs) modulate the voltage dependence of voltage-gated ion channels. As an important consequence thereof, PUFAs can suppress epileptic seizures and cardiac arrhythmia. However, molecular details for the interaction between PUFA and ion channels are not well understood. In this study, we have localized the site of action for PUFAs on the voltage-gated Shaker K channel by introducing positive charges on the channel surface, which potentiated the PUFA effect. Furthermore, we found that PUFA mainly affects the final voltage sensor movement, which is closely linked to channel opening, and that specific charges at the extracellular end of the voltage sensor are critical for the PUFA effect. Because different voltage-gated K channels have different charge profiles, this implies channel-specific PUFA effects. The identified site and the pharmacological mechanism will potentially be very useful in future drug design of small-molecule compounds specifically targeting neuronal and cardiac excitability.
引用
收藏
页码:563 / 577
页数:15
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