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Lipoelectric Modification of Ion Channel Voltage Gating by Polyunsaturated Fatty Acids
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Lipoelectric Modification of Ion Channel Voltage Gating by Polyunsaturated Fatty Acids
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Journal Article
Lipoelectric Modification of Ion Channel Voltage Gating by Polyunsaturated Fatty Acids
2008
Overview
Polyunsaturated fatty acids (PUFAs) have beneficial effects on epileptic seizures and cardiac arrhythmia. We report that
ω-3 and
ω-6
all-cis-PUFAs affected the voltage dependence of the
Shaker K channel by shifting the conductance versus voltage and the gating charge versus voltage curves in negative direction along the voltage axis. Uncharged methyl esters of the PUFAs did not affect the voltage dependence, whereas changes of pH and charge mutations on the channel surface affected the size of the shifts. This suggests an electrostatic effect on the channel's voltage sensors. Monounsaturated and saturated fatty acids, as well as
trans-PUFAs did not affect the voltage dependence. This suggests that fatty acid tails with two or more
cis double bonds are required to place the negative carboxylate charge of the PUFA in a position to affect the channel's voltage dependence. We propose that charged lipophilic compounds could play a role in regulating neuronal excitability by electrostatically affecting the channel's voltage sensor. We believe this provides a new approach for pharmacological treatment that is voltage sensor pharmacology.
Publisher
Elsevier Inc,Biophysical Society,The Biophysical Society
Subject
/ Animals Docosahexaenoic Acids/metabolism Electrophysiology Fatty Acids
/ Channels
/ Channels, Receptors, and Electrical Signaling
/ Charge
/ Docosahexaenoic Acids - metabolism
/ Esters
/ Fatty Acids, Unsaturated - analysis
/ Fatty Acids, Unsaturated - physiology
/ Ion Channel Gating - physiology
/ Ions
/ Lipids
/ MEDICIN
/ MEDICINE
/ Sensors
/ Shaker Superfamily of Potassium Channels - physiology
/ Voltage
