title: Ca2+-dependent facilitation of Cav1.3 Ca2+ channels by densin and Ca2+/calmodulin-dependent protein kinase II.
abstract: Ca(v)1 (L-type) channels and calmodulin-dependent protein kinase II (CaMKII) are key regulators of Ca(2+) signaling in neurons. CaMKII directly potentiates the activity of Ca(v)1.2 and Ca(v)1.3 channels, but the underlying molecular mechanisms are incompletely understood. Here, we report that the CaMKII-associated protein densin is required for Ca(2+)-dependent facilitation of Ca(v)1.3 channels. While neither CaMKII nor densin independently affects Ca(v)1.3 properties in transfected HEK293T cells, the two together augment Ca(v)1.3 Ca(2+) currents during repetitive, but not sustained, depolarizing stimuli. Facilitation requires Ca(2+), CaMKII activation, and its association with densin, as well as densin binding to the Ca(v)1.3 alpha(1) subunit C-terminal domain. Ca(v)1.3 channels and densin are targeted to dendritic spines in neurons and form a complex with CaMKII in the brain. Our results demonstrate a novel mechanism for Ca(2+)-dependent facilitation that may intensify postsynaptic Ca(2+) signals during high-frequency stimulation.
authors.affiliation: Department of Pharmacology, Emory University, Atlanta, Georgia 30322, USA.
authors.forename: Meagan A
authors.initials: MA
authors.lastname: Jenkins
authors.forename: Carl J
authors.initials: CJ
authors.lastname: Christel
authors.forename: Yuxia
authors.initials: Y
authors.lastname: Jiao
authors.forename: Sunday
authors.initials: S
authors.lastname: Abiria
authors.forename: Kristin Y
authors.initials: KY
authors.lastname: Kim
authors.forename: Yuriy M
authors.initials: YM
authors.lastname: Usachev
authors.forename: Gerald J
authors.initials: GJ
authors.lastname: Obermair
authors.forename: Roger J
authors.initials: RJ
authors.lastname: Colbran
authors.forename: Amy
authors.initials: A
authors.lastname: Lee
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000235:genetics / Q000378:metabolism*; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000378:metabolism*; D002460:Cell Line; D002478:Cells, Cultured; D049229:Dendritic Spines / Q000201:enzymology / Q000378:metabolism; D006624:Hippocampus / Q000201:enzymology / Q000378:metabolism; D006801:Humans; D008564:Membrane Potentials / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D009474:Neurons / Q000201:enzymology / Q000378:metabolism; D051381:Rats; D012795:Sialoglycoproteins / Q000378:metabolism*; D014162:Transfection
chemical_list: D015220:Calcium Channels; C504463:Lrrc7 protein, rat; D012795:Sialoglycoproteins; C093712:Cacna1d protein, rat; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D002118:Calcium
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