Format

Send to

Choose Destination
J Gen Physiol. 2011 Jun;137(6):563-77. doi: 10.1085/jgp.201110599.

An electrostatic potassium channel opener targeting the final voltage sensor transition.

Author information

1
Department of Clinical and Experimental Medicine, Division of Cell Biology, Linköping University, Sweden.

Abstract

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.

PMID:
21624947
PMCID:
PMC3105513
DOI:
10.1085/jgp.201110599
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center