KIR2.4 - A NOVEL K+ INWARD RECTIFIER CHANNEL ASSOCIATED WITH MOTONEURONS OF CRANIAL NERVE NUCLEI

Members of the Kir2 subfamily of inwardly rectifying K+ channels chara cterized by their strong current rectification are widely expressed bo th in the periphery and in the CNS in mammals. We have cloned from rat brain a fourth subfamily member, designated Kir2.4 (IRK4), which shar es 53-63% similarity to Kir2.1, Kir2.2, or Kir2.3 on the amino acid le vel. In situ hybridization analysis identifies Kir2.4 as the most rest ricted of all Kir subunits in the brain. Kir2.4 transcripts are expres sed predominantly in motoneurons of cranial nerve motor nuclei within the general somatic and special visceral motor cell column and thus ar e uniquely related to a functional system. Heterologous expression of Kir2.4 in Xenopus oocytes and mammalian cells gives rise to low-conduc tance channels (15 pS), with an affinity to the channel blockers Ba2(K-i = 390 mu M) and Cs+ (K-i = 8.06 mM) 30-50-fold lower than in othe r Kir channels. Low Ba2+ sensitivity allows dissection of Kir2.4 curre nts from other Kir conductances in hypoglossal motoneurons (HMs) in ra t brainstem slices. The finding that Ba2+-mediated block of Kir2.4 in HMs evokes tonic activity and increases the frequency of induced spike discharge indicates that Kir2.4 channels are of major importance in c ontrolling excitability of motoneurons in situ.