Identification and characterization of Cs+‐permeable K+ channel current in mouse cerebellar Purkinje cells in lobules 9 and 10 evoked by molecular layer stimulation

Abstract

The mouse cerebellum consists of 10 lobules, which are distinguishable by their anatomical and functional properties. However, the differences in the slow postsynaptic currents (sPSCs) of Purkinje cells between lobules have not been well studied. We recorded the sPSCs of lobules 3, 9 and 10 evoked by tetanic stimulation of the molecular layer in cerebellar slices, and found a novel outward sPSC mediated by the GABA(B) receptor in loblues 9 and 10 but hardly at all in lobule 3. We showed that the lobule-specific difference is at least partly attributable to differences in the density of GABAergic neurons (higher in lobule 10 than in lobules 3 and 9), and the functional expression level of postsynaptic GABA(B) receptor currents (larger in lobules 9 and 10 than in lobule 3). The G-protein-coupled inward rectifying K(+) channel (GIRK) is known to be activated by GABA(B) receptors; however, the outward sPSC was not blocked by a GIRK blocker, was not sensitive to Cs(+) block, and was observed when Cs(+) was used as a charge carrier. These results suggest that a K(+) channel other than GIRK could be activated by GABA(B) receptors. KCNK13 is a Cs(+)-permeable K(+) channel that shows intense expression of mRNA in Purkinje cells. KCNK13 current was enhanced by co-expression of G(βγ) subunits and was observed when Cs(+) was used as a charge carrier in heterologous expression systems, and the amino acids critical for these features were identified by mutagenesis. Taken together, these results show that KCNK13 is a legitimate candidate for the Cs(+)-permeable K(+) channel activated by GABA(B) receptors, presumably via G(βγ) subunits in Purkinje cells.