Heterooligomeric assembly of inward-rectifier K+ channels from subunits of different subfamilies: K(ir)2.1 (IRK1) and K(ir)4.1 (BIR10)

Activities of strong inward-rectifier K+ channels composed of K(ir)2.1 (84M), K(ir)2.1 (84T) and K(ir)4.1 subunits and weak inward-rectifier K+ channels composed of K(ir)4.1 (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 K(ir)2.1 channel types while it was monophasic for both K(ir)4.1 channel types. The release of blocking Mg2+ ions was slow for K(ir)2.1 (84T) but virtually instantaneous for K(ir)2.1( 84M) and both K(ir)4.1 channel types. Coexpression of K(ir)2.1 (84T) and K(ir)4.1 (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 K(ir)4.1(E158N) channels, while release of the block was almost instantaneous, similar to that for K(ir)4.1(E158N) channels. This suggests preferential formation of a particular heterooligomer such as was recently proposed for subunits within the K(ir)3.0 family.