Gating model for Kir4.1/Kir5.1 channel. (A) Representative Kir4.1/Kir5.1 currents as described for Fig. 2. The red and blue traces display the currents when the test pulses were −100 and +100 mV, respectively (which are shown at the right of D to illustrate the channel gating behavior). (B) Normalized I-V relationships measured at the start and at the end of the test pulses and normalized to the amplitude of the current recorded at −140 mV. (C) Ratio I_end/I_start as a function of the test pulse potentials. n = 8 cells. (D) Hypothetical model of the Kir4.1/Kir5.1 gating mechanism operated by the K⁺-flux. For clarity, two of the four channel subunits are depicted with the ion permeation path between them. The channel activation gate is represented by a hinge. According to the model, inward currents elicited by hyperpolarizing pulses induce the opening of the gate, whereas depolarizing pulses deactivate (to varying degrees) the channel. The partial deactivation of the channels observed at voltages negative to E_K could be either because the gate partially closes or due to a decrease in the channel open probability. Please see a detailed explanation of the hypothetical model in the Discussion section.