Delayed rectifier outward K+ current mediates the migration of rat cerebellar granule cells stimulated by melatonin.
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 MT(3)R, but were eliminated by the application of the MT(2)R 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.
Liu
Lin-Yun
LY
Institutes of Brain Science, School of Life Sciences and State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai, China.
Hoffman
Gloria E
GE
Fei
Xiao-Wei
XW
Li
Zheng
Z
Zhang
Zhi-Hong
ZH
Mei
Yan-Ai
YA
D000818:Animals; D000831:Animals, Newborn; D003994:Bucladesine / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D002525:Cerebellar Cortex / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism*; D017077:Culture Media, Conditioned / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D008550:Melatonin / Q000378:metabolism* / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D008959:Models, Neurological; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009924:Organ Culture Techniques; D018408:Patch-Clamp Techniques; D026902:Potassium Channel Blockers / Q000494:pharmacology; D024642:Potassium Channels, Voltage-Gated / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D044123:Receptor, Melatonin, MT2 / Q000037:antagonists & inhibitors / Q000378:metabolism; D044094:Receptors, Melatonin / Q000037:antagonists & inhibitors / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology
D017077:Culture Media, Conditioned; D026902:Potassium Channel Blockers; D024642:Potassium Channels, Voltage-Gated; D044123:Receptor, Melatonin, MT2; D044094:Receptors, Melatonin; D003994:Bucladesine; D000242:Cyclic AMP; D008550:Melatonin