T-type calcium channels regulate cortical plasticity in-vivo. [corrected].
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.
Uebele
Victor N
VN
Department of Sleep Research, Merck Research Laboratories, Philadelphia, Pennsylvania, USA.
Nuss
Cindy E
CE
Santarelli
Vincent P
VP
Garson
Susan L
SL
Kraus
Richard L
RL
Barrow
James C
JC
Stauffer
Shaun R
SR
Koblan
Kenneth S
KS
Renger
John J
JJ
Aton
Sara
S
Seibt
Julie
J
Dumoulin
Michelle
M
Jha
Sushil K
SK
Coleman
Tammi
T
Frank
Marcos G
MG
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*
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