We have cloned the human genes encoding the inwardly rectifying K+ (Ki
r) channel subunits, Kir2.2 (hKir2.2) and its variant, termed hKir2.2v
. When expressed in Xenopus oocytes, hKir.2 produced strong inwardly r
ectifying K+ currents, whereas the expression of hKir2.2v did not elic
it significant currents. Coexpression of hKir2.2v with hKir2.2 showed
an hKir2.2v inhibition of hKir2.2 K+ currents, indicating that it acts
as a negative regulator of hKir2.2 channel activity, Mutational analy
sis of hKir2.2v and studies of chimeras between hKir2.2 and hKir2.2v s
uggest that the intracellular C-terminal region of hKir2.2v participat
es in the negative regulation of the hKir2.2v channel activity.