Graphical abstract
Permeation mechanisms through the selectivity filter (SF) and helix bundle crossing (HBC) gate of GIRK2 channel. Water and K
+
ions co-translocate through the SF in a water-K
+
coupled manner from the extracellular matrix into the intracellular side with the aid of an external electric field. A tilt of the SF affects its recognition efficiency. A 4-K
+
occupancy in the SF-HBC cavity is required for the permeation through an open HBC; whilst the three K
+
ions around E152 help to abolish the unfavorable cation-dipole interactions to overcome the energy barrier; the fourth K
+
near HBC gets ready for the inward transport.
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