2014/10/06 by Richard K. Hite, Joel A. Butterwick, Roderick MacKinnon · 1 citation
Biochemistry, Genetics and Molecular Biology · Neuroscience · #Ion channel regulation and function #Lipid Membrane Structure and Behavior #Neuroscience and Neuropharmacology Research
paper · doi:10.7554/elife.04366
openalex publication_date 2014/10/06 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/28
Membrane phospholipids can function as potent regulators of ion channel function. This study uncovers and investigates the effect of phosphatidic acid on Kv channel gating. Using the method of reconstitution into planar lipid bilayers, in which protein and lipid components are defined and controlled, we characterize two effects of phosphatidic acid. The first is a non-specific electrostatic influence on activation mediated by electric charge density on the extracellular and intracellular membrane surfaces. The second is specific to the presence of a primary phosphate group, acts only through the intracellular membrane leaflet and depends on the presence of a particular arginine residue in the voltage sensor. Intracellular phosphatidic acid accounts for a nearly 50 mV shift in the midpoint of the activation curve in a direction consistent with stabilization of the voltage sensor's closed conformation. These findings support a novel mechanism of voltage sensor regulation by the signaling lipid phosphatidic acid.