IRK(1-3) AND GIRK(1-4) INWARDLY RECTIFYING K-RNAS ARE DIFFERENTIALLY EXPRESSED IN THE ADULT-RAT BRAIN( CHANNEL MESSENGER)

Molecular cloning together with functional characterization has shown that the newly identified family of inwardly rectifying K+ channels co nsists of several closely related members encoded by separate genes. I n this report we demonstrate the differential mRNA expression and dera iled cellular localization in the adult rat brain of seven members of the IRK and GIRK subfamilies. Using both radiolabeled cRNA riboprobes and specific oligonucleotide probes directed to nonconserved regions o f both known and newly isolated rat brain cDNAs, in situ hybridization revealed wide distribution with partly overlapping expression of the mRNAs of IRK1-3 and GIRK1-4. Except for the low levels of GIRK4 transc ripts observed, the overall distribution patterns of the other GIRK su bunits were rather similar, with high levels of expression in the olfa ctory bulb, hippocampus, cortex, thalamus, and cerebellum. Marked diff erences in expression levels existed only in some thalamic, brainstem, and midbrain nuclei, e.g., the substantia nigra, superior colliculus, or inferior olive. In contrast, IRK subunits were expressed more diff erentially: all mRNAs were abundant in dentate gyrus, olfactory bulb, caudate putamen, and piriform cortex. IRK1 and IRK3 were restricted to these regions, but they were absent from most parts of the thalamus, cerebellum, and brainstem, where IRK2 was expressed predominantly. Bec ause channel subunits may assemble as heteromultimers, additional func tional characterization based on overlapping expression patterns may h elp to decipher the native K+ channels in neurons and glial cells.