Microscopic origin of gating current fluctuations in a potassium channel voltage sensor.
Voltage-dependent ion channels open and close in response to changes in membrane electrical potential due to the motion of their voltage-sensing domains (VSDs). VSD charge displacements within the membrane electric field are observed in electrophysiology experiments as gating currents preceding ionic conduction. The elementary charge motions that give rise to the gating current cannot be observed directly, but appear as discrete current pulses that generate fluctuations in gating current measurements. Here we report direct observation of gating-charge displacements in an atomistic molecular dynamics simulation of the isolated VSD from the KvAP channel in a hydrated lipid bilayer on the timescale (10-μs) expected for elementary gating charge transitions. The results reveal that gating-charge displacements are associated with the water-catalyzed rearrangement of salt bridges between the S4 arginines and a set of conserved acidic side chains on the S1-S3 transmembrane segments in the hydrated interior of the VSD.
Department of Chemistry, University of California, Irvine, California, USA.
J Alfredo
JA
Freites
Eric V
EV
Schow
Stephen H
SH
White
Douglas J
DJ
Tobias
D041522:Aeropyrum / Q000378:metabolism*; D019843:Archaeal Proteins / Q000737:chemistry / Q000378:metabolism*; D015640:Ion Channel Gating / Q000502:physiology*; D008564:Membrane Potentials / Q000502:physiology; D008853:Microscopy; D015221:Potassium Channels / Q000737:chemistry / Q000378:metabolism*; D017434:Protein Structure, Tertiary
D019843:Archaeal Proteins; D015221:Potassium Channels