ONTOGENY OF GENE-EXPRESSION OF KIR CHANNEL SUBUNITS IN THE RAT

We report the detailed gene expression of all subunits within the Kir2 and Kir3 inwardly rectifying K+ channel subfamilies in the developing rat. Using in situ hybridization, onset of expression and cellular di stribution of transcripts in embryonic and postnatal rat brains as wel l as in peripheral tissues is evaluated. Beginning at embryonic day 13 (E13), except ''forebrain'' Kir2.3 subunits which are absent from the body and brain until E21, all subunits appear with distinct and mainl y nonoverlapping expression patterns. During ontogenic development, ex pression in the CNS becomes more widespread, leading to widely overlap ping mRNA patterns as observed in the adult rat. Subunits are mainly f ound in regions of the developing brain that are also positive in the adult. Most subunits, in particular Kir3.2 and Kir3.4, are expressed t ransiently in distinct brain nuclei during ontogeny. Appearance of Kir transcripts is not generally related to the progressive and recessive phases during neurogenesis, but rather regulated differentially for e ach subunit and any specific group of neurons. It is demonstrated for the first time that several subunits, and most abundantly Kir2.2, are present early in the peripheral nervous system, i.e., in dorsal root-, sensory cranial-, and sympathetic ganglia. Also, of all subunits Kir3 .3 is ubiquitously expressed in the entire embryonic nervous system an d throughout the body. In summary, analysis of ontogenic Kir channel e xpression helps deciphering the importance of Kir channels (as exempli fied for the defective weaver Kir3.2 gene) during proliferation, diffe rentiation, and synaptogenesis in the CNS.