Mutations in the P-region of a mammalian potassium channel (RCK1): a comparison with the Shaker potassium channel.

Deletion mutants of Shaker K channels lacking the middlemost 2 residues of the amino acid sequence GYGD in their P-region lose K-selectivity and become functionally similar to voltage-activated Ca channels. Ca channel characteristics are also conferred on voltage-activated Na channels when residues K in domain III and/or A in domain IV in the P-region of the Na channel are replaced by E residues. In this study, we have investigated a possible evolutionary connection between voltage-activated K and Na channels. Mutant monomeric and multi-heteromeric RCK1 K channel cDNAs were made to match the residues at equivalent positions in the P-region of the Na channel. We found that in contrast to mutant Shaker K channels, the same mutants in RCK1 K channels did not yield functional expression. Therefore possible Na channel-like ion conduction properties conferred on K channels could not be demonstrated. However, our results show that the same mutations in highly homologous channels can produce different effects and point to hitherto unknown structural differences in the P-region of these homologous K channels. Therefore we conclude that extrapolation of the structural and functional importance of residues should be done with caution, even when ion channels belong to the same family.