SUBUNIT POSITIONAL EFFECTS REVEALED BY NOVEL HETEROMERIC INWARDLY RECTIFYING K+ CHANNELS

K-ir 4.1 is an inward rectifier potassium channel subunit isolated fro m rat brain which forms homomeric channels when expressed in Xenopus o ocytes; K-ir 5.1 is a structurally related subunit which does not. Co- injection of mRNAs encoding K-ir 4.1 and K-ir 5.1 resulted in potassiu m currents that (i) were much larger than those seen from expression o f K-ir 4.1 alone, (ii) increased rather than decreased during several seconds at strongly negative potentials and (iii) had an underlying un itary conductance of 43 pS rather than the 12 pS seen with K-ir 4.1 al one. In contrast, the properties of K-ir 1.1, 2.1, 2.3, 3.1, 3.2 or 3. 4 were not altered by coexpression with K-ir 5.1. Expression of a conc atenated cDNA encoding two or four linked subunits produced currents w ith the properties of co-expressed K-ir 4.1 and K-ir 5.1 when the subu nits were connected 4-5 or 4-5-4-5, but not when they were connected 4 -4-5-5, The results indicate that K-ir 5.1 associates specifically wit h K-ir 4.1 to form heteromeric channels, and suggest that they do so n ormally in the subunit order 4-5-4-5. Further, the relative order of s ubunits within the channel contributes to their functional properties.