title: Modulation of T-type Ca2+ channels by corticotropin-releasing factor through protein kinase C pathway in MN9D dopaminergic cells.
abstract: Corticotrophin-releasing factor (CRF) is the main regulator of the body's stress axis and its signal is translated through G-protein-coupled CRF receptors (CRF-R1, CRF-R2). Even though CRF receptors are present in the midbrain dopamine neurons, the cellular mechanism of CRF action is not clear yet. Since voltage-dependent Ca(2+) channels are highly expressed and important in dopamine neuronal functions, we tested the effect of CRF on voltage-dependent Ca(2+) channels in MN9D cells, a model of dopamine neurons. The application of CRF-related peptide, urocortin 1, reversibly inhibited T-type Ca(2+) currents, which was a major Ca(2+) channel in the cells. The effect of urocortin was abolished by specific CRF-R1 antagonist and was mimicked by protein kinase C (PKC) activator, phorbol 12-myristate 13-acetate. PKC inhibitors abolished the effect of urocortin. These results suggest that urocortin modulates T-type Ca(2+) channel by interacting with CRF-R1 via the activation of PKC signal pathway in MN9D cells.
authors.affiliation: Department of Physiology, Sungkyunkwan University School of Medicine, Suwon 440-746, South Korea.
authors.forename: Yonjung
authors.initials: Y
authors.lastname: Kim
authors.forename: Myoung Kyu
authors.initials: MK
authors.lastname: Park
authors.forename: Dae-Yong
authors.initials: DY
authors.lastname: Uhm
authors.forename: Sungkwon
authors.initials: S
authors.lastname: Chung
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D002478:Cells, Cultured; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D004594:Electrophysiology; D005786:Gene Expression Regulation; D051379:Mice; D009474:Neurons / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism*; D015398:Signal Transduction; D013755:Tetradecanoylphorbol Acetate / Q000737:chemistry; D013997:Time Factors; D054832:Urocortins
chemical_list: D054832:Urocortins; D003346:Corticotropin-Releasing Hormone; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium; D004298:Dopamine