Melatonin (MT) may work as a neuromodulator through the associated MT receptors in the central nervous system. Previously, our studies have shown that MT increased the I-K current via a G protein-related pathway. In the present study, patch-clamp whole-cell recording, transwell migration assays and organotypic cerebellar slice cultures were used to examine the effect of MT on granule cell migration. MT increased the I-K current amplitude and migration of granule cells. Meanwhile, TEA, the I-K channel blocker, decreased the I-K current and slowed the migration of granule cells. Furthermore, the effects of MT on the I-K current and cell migration were not abolished by pre-incubation with P7791, a specific antagonist of MT3R, but were eliminated by the application of the MT2R antagonists K185 and 4-P-PDOT. I-K current and cell migration were decreased by the application of dibutyryl cyclic AMP (dbcAMP), which was in contrast to the MT effect on the I-K current and cell migration. Incubation with dbcAMP essentially blocked the MT-induced increasing effect. Moreover, incubation of isolated cell cultures in the MT-containing medium also decreased the cAMP immunoreactivity in the granule cells. It is concluded, therefore, that I-K current, downstream of a cAMP transduction pathway, mediates the migration of rat cerebellar granule cells stimulated by MT.
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