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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Calcium Channel Blockers / pharmacology
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Calcium Channels, T-Type / drug effects
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Calcium Channels, T-Type / metabolism*
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Cats
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Cell Line
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Dominance, Ocular / drug effects
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Dominance, Ocular / physiology*
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Humans
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Indoles / pharmacology
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Membrane Potentials / drug effects
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Membrane Potentials / physiology
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Neuronal Plasticity / drug effects
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Neuronal Plasticity / physiology*
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Patch-Clamp Techniques
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Sensory Deprivation / physiology
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Triazoles / pharmacology
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Vision, Monocular / physiology*
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Visual Cortex / drug effects
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Visual Cortex / metabolism*
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Visual Pathways / drug effects
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Visual Pathways / metabolism
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Visual Perception / drug effects
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Visual Perception / physiology*
Substances
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Calcium Channel Blockers
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Calcium Channels, T-Type
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Indoles
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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
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Triazoles