Gating properties of inward-rectifier potassium channels: Effects of permeant ions

Two inward-rectifier K+ channels, ROMK2 (Kir1.1b) and IRK I (Kir2.1), were expressed in Xenopus oocytes and their gating properties were studied in ce ll-attached membrane patches. The gating properties depended strongly on th e ion being conducted (K+, NH4+, Rb+, or Tl+), suggesting tight coupling be tween permeation and gating. Mean open times were strongly dependent on the nature of the conducted ion. For ROMK2 the order from the longest to the s hortest times was K+ > Rb+ > Tl+ > NH4+. For IRK1 the sequence was K+ > NH4 + > Tl+. In both cases the open times decreased monotonically as the membra ne voltage was hyperpolarized. Both the absolute values and the voltage dep endence of closed times were dependent on the conducted species. ROMK2 show ed a single closed state whose mean lifetimes were biphasic functions of vo ltage. The maxima were at various voltages for different ions. IRK1 had at least two closed states whose lifetimes decreased monotonically with K+, in creased monotonically with Tl+ and were relatively constant with NH4+ as th e conducted ion. We explain the ion-dependence of gating by assuming that t he ions bind to a site within the permeation pathway, resulting in a stable , ion-dependent, closed state of the channel. The patterns of voltage-depen dence of closed-state lifetimes, which are specific for different ions, can be explained by variations in the rate at which the bound ions leave the p ore toward the inside or the outside of the cell.