HETEROOLIGOMERIC ASSEMBLY OF INWARD-RECTIFIER K- K(IR)2.1 (IRK1) AND K(IR)4.1 (BIR10)( CHANNELS FROM SUBUNITS OF DIFFERENT SUBFAMILIES )

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/vo ltage (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 slo w for K(ir)2.1 (84T) but virtually instantaneous for K(ir)2.1( 84M) an d 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 sig nificantly different from that of either parental homooligomeric chann el type. Block by intracellular Mg2+ was markedly stronger than that f or K(ir)4.1(E158N) channels, while release of the block was almost ins tantaneous, similar to that for K(ir)4.1(E158N) channels. This suggest s preferential formation of a particular heterooligomer such as was re cently proposed for subunits within the K(ir)3.0 family.