Gating Current Models Computed with Consistent Interactions

Abstract

Quantum calculations on the VSD of Kv1.2 (3Lut pdb coordinates) show several water molecules move into the VSD when the sign of the electric field goes from positive intracellularly to negative (closed). The protein backbone remains essentially immobile; S4 does not move vertically with respect to the other transmembrane segments, but may have minimal horizontal motion (parallel to the membrane surface, were the membrane included in the calculation); side chain rearrangements, however, change some intramolecular distances. We have calculated the dipole moments of the optimized structures for several cases, as well as the structures of the water clusters (these calculations:18 water molecules, 373 atoms from the protein, from the 2nd to the 4th arginine in S4, and the complementary sections of S1, S2, and S3). Rotating two water molecules in the cluster (closed conformation) sufficed for a significant change in dipole (in most calculations, counting the dipole for the entire system; dipole changes with state as well, %5 D for the open configuration, approximately an order of magnitude more when closed, suggesting dipole shift is part of the sensing mechanism). Several energy minima were determined; the closed configurations were several kT lower in energy than open configurations. The water behavior resembled a phase change, with finite DV (volume) in its overall shift in structure with changes in electric field; there is more than one energy minimum, but the change in water density is unambiguous, although the water is not ordered in either case. Gating is coupled to water via a proton shift in the lower section of the VSD (see our other abstract).

Gating currents

“…It should be noted, however, that these models are not based on physical parameters of the structure that generate the gating currents, and they are not self-consistent in the sense that the movement of the gating particle does not affect the distribution of the electric field or other charged species in the system. A physical self-consistent model based on the known structure of a voltage sensor has been recently developed, and it gives insight on the interaction of the gating charges, electric field, and displacement currents (Horng et al, 2016(Horng et al, , 2017.…”

“…Therefore, with this type of model, the prediction of the physical charges moving may not reflect the actual charge moving. On the other hand, a physical model based on the structure of a voltage sensor like that developed by Horng et al (2016Horng et al ( , 2017 is self-consistent and includes both current density and displacement currents. Using this model, it was shown that even though all the physical charges translocate across the entire electric field, the charge estimated in the external circuit is less than the physical charge moved, because some of the total current is displacement current in the sensor.…”

Maxwell Equations without a Polarization Field, Using a Paradigm from Biophysics

“…The voltage and time dependence arises from the molecular motions underlying the gating current. The voltage and time dependence defines the mean molecular motions [ 7 , 16 , 17 , 19 , 21 , 82 , 83 , 84 , 85 , 86 ] and is called ‘the gating current’ in the biophysics literature.…”

Asking biological questions of physical systems: The device approach to emergent properties

“…Physiologists have shown that many systems in biology are modular and function as devices with definite outputs controlled by specific inputs according to robust rules. The outputs are typically on a large scale than the inputs so a few devices in series serves to link the smallest input (say the atoms of the voltage sensor of channel [24] or of a selectivity filter [25,26] to macroscopic function. The atoms of the selectivity filter control the current through the open channel in one device.…”