The mechanism of inward rectification in Kir channels: A novel kinetic model with non-equilibrium thermodynamics approach

Nonequilibrium Thermodynamics of Ion Flux through Membrane Channels

“…The current-voltage relationship shifts parallel to the same amount as the equilibrium potential shifts, as the extracellular or intracellular K + concentration changes. The inward rectification has been attributed to the "driving force"-dependent or flux-coupled block, which means that the movement and thus the apparent binding rate of the blocker is coupled by the direction of K + flux, so the apparent affinity of the intracellular blocker is influenced by the driving force for K + ion conduction [1,2]. The elongated narrow long cytoplasmic pore in the Kir channel extends the single-file pathway to 60 Å [32,33], and thus facilitates the flux-coupling between the conducting K + ion flux and the blocker in the multi-ion cytoplasmic pore.…”

“…When (V m − V eq ) < 0, the K + flux is predominantly inward, and the inner K + ions in the cytoplasmic pore always preclude the intracellular blocker from entering to the pore, so no blockage occurs. The strong inward rectification results from the steep changes in the direction and flux ratio of the K + ion flux near the equilibrium potential [1,2]. the multi-ion cytoplasmic pore.…”

“…The strands presentation of the Kir2.1 channel is retrieved from the SWISS-MODEL Repository based on the X-ray crystallography template structure of a Kir2.2 channel (PDB: 3sph) [34]; (b) The current-voltage relationship of the Kir channel at symmetrical K + concentrations (V eq = 0 mV) in the presence of the intracellular blocker. The strong inward rectification results from the "driving force"-dependent or flux-coupled block by the intracellular blocker [1,2].…”

“…The driving force can also couple other specific biophysical processes or biochemical reactions under certain circumstances. For example, the "driving force"-dependent or flux-coupled block is essential to the inward rectification in the inward rectifier K + channels [1,2]. The protons flow down the electrochemical potential gradient through the F O portion of ATP synthase on the mitochondrial membrane drives the synthesis of ATP [3][4][5][6].…”