Mechanism of Rectification in Inward-Rectifier K+ Channels¹

Inward rectifiers are a class of K⁺ channels that can conduct much larger inward currents at membrane voltages negative to the K⁺ equilibrium potential than outward currents at voltages positive to it, even when K⁺ concentrations on both sides of the membrane are made equal. This conduction property, called inward rectification, enables inward rectifiers to perform many important physiological tasks. Rectification is not an inherent property of the channel protein itself, but reflects strong voltage dependence of channel block by intracellular cations such as Mg²⁺ and polyamines. This voltage dependence results primarily from the movement of K⁺ ions across the transmembrane electric field along the pore, which is energetically coupled to the blocker binding and unbinding. This mutual displacement mechanism between several K⁺ ions and a blocker explains the signature feature of inward rectifier K⁺ channels, namely, that at a given concentration of intracellular K⁺, their macroscopic conductance depends on the difference between membrane voltage and the K⁺ equilibrium potential rather than on membrane voltage itself.