title: T-type calcium channels regulate cortical plasticity in-vivo. [corrected].
abstract: T-type voltage-dependent calcium channels may play an important role in synaptic plasticity, but lack of specific antagonists has hampered investigation into this possible function. We investigated the role of the T-type channel in a canonical model of in-vivo cortical plasticity triggered by monocular deprivation. We identified a compound (TTA-I1) with subnanomolar potency in standard voltage clamp assays and high selectivity for the T-type channel. When infused intracortically, TTA-I1 reduced cortical plasticity triggered by monocular deprivation while preserving normal visual response properties. These results show that the T-type calcium channel plays a central role in cortical plasticity.
authors.affiliation: Department of Sleep Research, Merck Research Laboratories, Philadelphia, Pennsylvania, USA.
authors.forename: Victor N
authors.initials: VN
authors.lastname: Uebele
authors.forename: Cindy E
authors.initials: CE
authors.lastname: Nuss
authors.forename: Vincent P
authors.initials: VP
authors.lastname: Santarelli
authors.forename: Susan L
authors.initials: SL
authors.lastname: Garson
authors.forename: Richard L
authors.initials: RL
authors.lastname: Kraus
authors.forename: James C
authors.initials: JC
authors.lastname: Barrow
authors.forename: Shaun R
authors.initials: SR
authors.lastname: Stauffer
authors.forename: Kenneth S
authors.initials: KS
authors.lastname: Koblan
authors.forename: John J
authors.initials: JJ
authors.lastname: Renger
authors.forename: Sara
authors.initials: S
authors.lastname: Aton
authors.forename: Julie
authors.initials: J
authors.lastname: Seibt
authors.forename: Michelle
authors.initials: M
authors.lastname: Dumoulin
authors.forename: Sushil K
authors.initials: SK
authors.lastname: Jha
authors.forename: Tammi
authors.initials: T
authors.lastname: Coleman
authors.forename: Marcos G
authors.initials: MG
authors.lastname: Frank
mesh_terms: D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020747:Calcium Channels, T-Type / Q000187:drug effects / Q000378:metabolism*; D002415:Cats; D002460:Cell Line; D023882:Dominance, Ocular / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology*; D018408:Patch-Clamp Techniques; D012683:Sensory Deprivation / Q000502:physiology; D014230:Triazoles / Q000494:pharmacology; D015349:Vision, Monocular / Q000502:physiology*; D014793:Visual Cortex / Q000187:drug effects / Q000378:metabolism*; D014795:Visual Pathways / Q000187:drug effects / Q000378:metabolism; D014796:Visual Perception / Q000187:drug effects / Q000502:physiology*
chemical_list: D002121:Calcium Channel Blockers; D020747:Calcium Channels, T-Type; D007211:Indoles; C543303:N-(4-fluorobenzyl)-1-(3-(5-(1H-1,2,4-triazol-1-ylmethyl)-1H-indol-3-yl)propyl)-N-(2,2,2-trifluoroethyl)piperidin-4-amine; D014230:Triazoles