An electrostatic potassium channel opener targeting the final voltage-sensor transition
2011 (English)In: The Journal of General Physiology, ISSN 0022-1295, Vol. 137, no 6, 563-577 p.Article in journal (Refereed) Published
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. We furthermore 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.
Place, publisher, year, edition, pages
The Rockefeller University Press , 2011. Vol. 137, no 6, 563-577 p.
Docosahexaenoic acid, ketogenic diet, voltage clamp, Xenopus oocytes
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:liu:diva-68083DOI: 10.1085/jgp.201110599ISI: 000291047100008OAI: oai:DiVA.org:liu-68083DiVA: diva2:416140
Sara I Börjesson and Fredrik Elinder, An electrostatic potassium channel opener targeting the final voltage-sensor transition, 2011, The Journal of General Physiology, (137), 6, 563-577.
Licensee: The Rockefellow University Press