Gating-Induced Large Aqueous Volumetric Remodeling And Aspartate Tolerance In The Voltage Sensor Domain Of Shaker K+ Channels

Significance The neuronal action potential is a self-propagating transient depolarization traveling along the neuron membrane. This signal is produced by the coordinated activation of voltage-gated ion channels (VGCs), a family of ion-selective transmembrane proteins activated by depolarization. Sodium and calcium VGCs reinforce the signal, while potassium VGCs terminate it. A conserved voltage sensor domain (VSD) in VGCs responds with an unresolved conformational change driven by the transmembrane electrophoretic displacements of four arginine side chains. We show that those arginine side chains are stabilized by water impregnating the VSD and that, upon activation, displace large and dissimilar aqueous volumes at both protein faces. This charge translocation entails a transporter-like remodeling of water–protein interfaces that should create mechanical spikes accompanying action potentials.