TY - JOUR TI - Phosphatidic acid modulation of Kv channel voltage sensor function AU - Hite, Richard K AU - Butterwick, Joel A AU - MacKinnon, Roderick A2 - Aldrich, Richard VL - 3 PY - 2014 DA - 2014/10/06 SP - e04366 C1 - eLife 2014;3:e04366 DO - 10.7554/eLife.04366 UR - https://doi.org/10.7554/eLife.04366 AB - 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. KW - ion channel KW - electrophysiology KW - voltage-gated potassium channel JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -