Key result
Densin functionally recruits CaMKII to Cav1.3 channels, causing frequency-dependent facilitation of Cav1.3 Ca2+ signals during repetitive depolarizing stimuli.
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The study identifies a novel molecular mechanism where densin and CaMKII cooperate to facilitate Ca(v)1.3 Ca(2+) channels during high-frequency stimulation in neurons.
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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Jenkins et al. (2010) studied this question. Coexpression of densin and CaMKII vs. Cav1.3 alone or with either densin or CaMKII alone was evaluated on Ca2+-dependent facilitation of Cav1.3 Ca2+ currents during repetitive depolarizing stimuli. Densin functionally recruits CaMKII to Cav1.3 channels, causing frequency-dependent facilitation of Cav1.3 Ca2+ signals during repetitive depolarizing stimuli.
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