[K+] Dependence of open-channel conductance in cloned inward rectifier potassium channels (IRK1, Kir2.1)

Potassium conduction through unblocked inwardly rectifying (IRK1, Kir2.1) potassium channels was measured in inside-out patches from Xenopus oocytes, after removal of polyamine-induced strong inward rectification-unblocked IRK1 channel current-voltage (I-V) relations show very mild inward rectification in symmetrical solutions, are linearized in nonsymmetrical solutions that bring the K+ reversal potential to extreme negative values, and follow Goldman-Hodgkin-Katz constant field equation at extreme positive E(K). When intracellular K+ concentration (K-IN) was varied, at constant extracellular K+ concentration (K-OUT) the conductance at the reversal potential (G(REV)) followed closely the predictions of the Goldman-Hodgkin-Katz constant field equation at low concentrations and saturated sharply at concentrations of > 150 mM. Similarly, when K-OUT was varied, at constant K-IN, G(REV) saturated at concentrations of > 150 mM. A square-root dependence of conductance on K-OUT is a well-known property of inward rectifier potassium channels and is a property of the open channel. A nonsymmetrical two-site three-barrier model can qualitatively explain both the I-V relations and the [K+] dependence of conductance of open IRK1 (Kir2.1) channels.