Co-expression of human Kir3 subunits can yield channels with different functional properties

To date, no comprehensive study has been done on all combinations of the hu man homologues of the Kir3.0 channel family, and the human homologue of Kir 3.3 has not yet been identified. To obtain support for the contention that most of the functional data on non-human Kir3.0 channels can be extrapolate d to human channels, we have cloned the human homologues of the Kir3.0 fami ly, including the yet unidentified human Kir3.3, and the human Kir 4.1. The expression pattern of these channels in various human brain areas and peri pheral tissues, analysed by Northern blot analysis, allows for the existenc e of various homomeric and heteromeric forms of human Kir3.0 channels. Expr ession studies of all possible combinations in Xenopus oocytes indicated th at in homomeric Kir3.2c and heteromeric Kir3.1/3.2c channels mediate, in ou r studies, inward currents with largest amplitude of any other Kir3.0 chann el combinations, followed by heteromeric Kir3.1/3.4 and homomeric Kir4.1 ch annels. Channel combinations which include Kir3.3 are detrimental to the fo rmation of functional channels. The co-expression experiments with differen t Kir channel subunits indicate the selective formation of certain channel combinations, suggesting that channel specificity is not solely dependent o n spatial and temporal regulation of Kir subunit expression.