Ca2+-dependent facilitation of Cav1.3 Ca2+ channels by densin and Ca2+/calmodulin-dependent protein kinase II

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 Ca...

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Published inThe Journal of neuroscience Vol. 30; no. 15; pp. 5125 - 5135
Main Authors Jenkins, Meagan A, Christel, Carl J, Jiao, Yuxia, Abiria, Sunday, Kim, Kristin Y, Usachev, Yuriy M, Obermair, Gerald J, Colbran, Roger J, Lee, Amy
Format Journal Article
LanguageEnglish
Published United States Society for Neuroscience 14.04.2010
Subjects
Animals
Calcium - metabolism
Calcium Channels - genetics
Calcium Channels - metabolism
Calcium-Calmodulin-Dependent Protein Kinase Type 2 - metabolism
Cell Line
Cells, Cultured
Dendritic Spines - enzymology
Dendritic Spines - metabolism
Hippocampus - enzymology
Hippocampus - metabolism
Humans
Membrane Potentials - physiology
Mice
Mice, Inbred BALB C
Neurons - enzymology
Neurons - metabolism
Rats
Sialoglycoproteins - metabolism
Transfection
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Summary: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.
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M.A.J. and C.J.C. contributed equally to this work.
ISSN:0270-6474
1529-2401
DOI:10.1523/jneurosci.4367-09.2010