Conduction through a narrow inward-rectifier K⁺ channel pore

Inwardly rectifying potassium (Kir) channels play a key role in controlling membrane potentials in excitable and unexcitable cells, thereby regulating a plethora of physiological processes. G-protein-gated Kir channels control heart rate and neuronal excitability via small hyperpolarizing outward K⁺ currents near the resting membrane potential. Despite recent breakthroughs in x-ray crystallography and cryo-EM, the gating and conduction mechanisms of these channels are poorly understood. MD simulations have provided unprecedented details concerning the gating and conduction mechanisms of voltage-gated K⁺ and Na⁺ channels. Here, we use multi-microsecond-timescale MD simulations based on the crystal structures of GIRK2 (Kir3.2) bound to phosphatidylinositol-4,5-bisphosphate to provide detailed insights into the channel's gating dynamics, including insights into the behavior of the G-loop gate. The simulations also elucidate the elementary steps that underlie the movement of K⁺ ions through an inward-rectifier K⁺ channel under an applied electric field. Our simulations suggest that K⁺ permeation might occur via direct knock-on, similar to the mechanism recently shown for K_v channels.