TY - JOUR T1 - Ca<sup>2+</sup>-Dependent Facilitation of Ca<sub>v</sub>1.3 Ca<sup>2+</sup> Channels by Densin and Ca<sup>2+</sup>/Calmodulin-Dependent Protein Kinase II JF - The Journal of Neuroscience JO - J. Neurosci. SP - 5125 LP - 5135 DO - 10.1523/JNEUROSCI.4367-09.2010 VL - 30 IS - 15 AU - Meagan A. Jenkins AU - Carl J. Christel AU - Yuxia Jiao AU - Sunday Abiria AU - Kristin Y. Kim AU - Yuriy M. Usachev AU - Gerald J. Obermair AU - Roger J. Colbran AU - Amy Lee Y1 - 2010/04/14 UR - http://www.jneurosci.org/content/30/15/5125.abstract N2 - 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 Ca2+ 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 Ca2+-dependent facilitation that may intensify postsynaptic Ca2+ signals during high-frequency stimulation. ER -