Cav1 (L-type) channels and calmodulin-dependent protein kinase II (CaMKII) are key regulators of Ca2+ signaling in neurons. CaMKII directly potentiates the activity of Cav1.2 and Cav1.3 channels, but the underlying molecular mechanisms are incompletely understood. Here, we report that the CaMKII-associated protein densin is required for Ca2+-dependent facilitation of Cav1.3 channels. While neither CaMKII nor densin independently affects Cav1.3 properties in transfected HEK293T cells, the two together augment Cav1.3 Ca 2+currents during repetitive, but not sustained, depolarizing stimuli. Facilitation requires Ca2+, CaMKII activation, and its association with densin, as well as densin binding to the Cav1.3 α1 subunit C-terminal domain. Cav1.3 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. Copyright ©2010 the authors.
CITATION STYLE
Jenkins, M. A., Christel, C. J., Jiao, Y., Abiria, S., Kim, K. Y., Usachev, Y. M., … Lee, A. (2010). Ca2+-Dependent facilitation of cav1.3 ca2+ channels by densin and ca2+/calmodulin-dependent protein kinase II. Journal of Neuroscience, 30(15), 5125–5135. https://doi.org/10.1523/JNEUROSCI.4367-09.2010
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