Modulation of Kv Channel Gating by Light-Controlled Membrane Thickness.

Abstract

Voltage-gated potassium (Kv) channels are e ssential for shaping action potentials and rely on anionic lipids for proper gating, yet the mechanistic basis of lipid-channel interactions remains unclear. Cryo-electron microscopy studies suggest that, in the down state, arginine residues of the voltage sensor draw lipid phosphates upward, leading to a local membrane thinning of ~5 Å-an effect absent in the open state. To test whether membrane thickness directly affects voltage sensor function, we reconstituted Kv channels from Aeropyrum pernix (KvAP) into planar lipid bilayers containing photoswitchable lipids. Upon blue light illumination, the membrane thickened, and KvAP activity increased; UV light reversed both effects. Our findings indicate that membrane thickening weakens the interaction between lipid phosphates and voltage-sensing arginines in the down state, lowering the energy barrier for the transition to the up state and thereby promoting channel opening. This non-genetic, membrane-mediated approach provides a new strategy to control ion channel activity using light and establishes a direct, reversible link between membrane mechanics and voltage sensing, with potential applications in the remote control of neuronal excitability.