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

Jenkins MA, Christel CJ, Jiao Y, Abiria S, Kim KY, Usachev YM, Obermair GJ, Colbran RJ, Lee A
J Neurosci. 2010 30 (15): 5125-35

PMID: 20392935 · PMCID: PMC2990970 · DOI:10.1523/JNEUROSCI.4367-09.2010

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.

MeSH Terms (16)

Animals Calcium Calcium-Calmodulin-Dependent Protein Kinase Type 2 Calcium Channels Cell Line Cells, Cultured Dendritic Spines Hippocampus Humans Membrane Potentials Mice Mice, Inbred BALB C Neurons Rats Sialoglycoproteins Transfection

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