Heterooligomeric assembly of inward-rectifier K+ channels from subunits of different subfamilies: Kir2.1 (IRK1) and Kir4.1 (BIR10).

Activities of strong inward-rectifier K+ channels composed of Kir2. 1(84 M), Kir2.1(84T) and Kir4.1 subunits and weak inward-rectifier K+ channels composed of Kir4.1(E158N) subunits were measured from giant inside-out patches of Xenopus laevis oocytes. The conductance/voltage (g/V) relationship for block by intracellular spermine (SPM) was biphasic for both Kir2.1 channel types while it was monophasic for both Kir4.1 channel types. The release of blocking Mg2+ ions was slow for Kir2.1(84T) but virtually instantaneous for Kir2.1(84M) and both Kir4.1 channel types. Coexpression of Kir2.1(84T) and Kir4.1(E158N) resulted in heterooligomeric channels which were strongly rectifying, with a g/V relationship for SPM-evoked block that was significantly different from that of either parental homooligomeric channel type. Block by intracellular Mg2+ was markedly stronger than that for Kir4.1(E158N) channels, while release of the block was almost instantaneous, similar to that for Kir4.1(E158N) channels. This suggests preferential formation of a particular heterooligomer such as was recently proposed for subunits within the Kir3.0 family.