Molecular cloning and functional expression of a novel brain‐specific inward rectifier potassium channel

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Abstract
We have cloned a novel brain‐specific inward rectifier K+ channel from a mouse brain cDNA library and designated it MB‐IRK3. The mouse brain cDNA library was screened using a fragment of the mouse macrophage inward rectifier K+ channel (IRK1) cDNA as a probe. The amino acid sequence of MB‐IRK3 shares 61% and 64% identity to MB‐IRK1 and RB‐IRK2, respectively.Xenopus oocytes injected with cRNA derived from this clone expressed a potassium current which showed inward‐rectifying channel characteristics similar to MB‐IRK1 and RB‐IRK2 currents, but distinct from ROMK1 or GIRK1 current. However, the single channel conductance of MB‐IRK3 was ∼ 10 pS with 140 mM extracellular K+, which was distinct from that of MB‐IRK1 (20 pS). MB‐IRK3 mRNA expressed specifically in the forebrain, which clearly differed from MB‐IRK1 and RB‐IRK2 mRNAs. These results indicate that members of the IRK family with distinct electrophysiological properties express differentially and may play heterogenous functional roles in brain functions.