Differential CaMKII regulation by voltage-gated calcium channels in the striatum.

Pasek JG, Wang X, Colbran RJ
Mol Cell Neurosci. 2015 68: 234-43

PMID: 26255006 · PMCID: PMC4593756 · DOI:10.1016/j.mcn.2015.08.003

Calcium signaling regulates synaptic plasticity and many other functions in striatal medium spiny neurons to modulate basal ganglia function. Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) is a major calcium-dependent signaling protein that couples calcium entry to diverse cellular changes. CaMKII activation results in autophosphorylation at Thr286 and sustained calcium-independent CaMKII activity after calcium signals dissipate. However, little is known about the mechanisms regulating striatal CaMKII. To address this, mouse brain slices were treated with pharmacological modulators of calcium channels and punches of dorsal striatum were immunoblotted for CaMKII Thr286 autophosphorylation as an index of CaMKII activation. KCl depolarization increased levels of CaMKII autophosphorylation ~2-fold; this increase was blocked by an LTCC antagonist and was mimicked by treatment with pharmacological LTCC activators. The chelation of extracellular calcium robustly decreased basal CaMKII autophosphorylation within 5min and increased levels of total CaMKII in cytosolic fractions, in addition to decreasing the phosphorylation of CaMKII sites in the GluN2B subunit of NMDA receptors and the GluA1 subunit of AMPA receptors. We also found that the maintenance of basal levels of CaMKII autophosphorylation requires low-voltage gated T-type calcium channels, but not LTCCs or R-type calcium channels. Our findings indicate that CaMKII activity is dynamically regulated by multiple calcium channels in the striatum thus coupling calcium entry to key downstream substrates.

Copyright © 2015 Elsevier Inc. All rights reserved.

MeSH Terms (20)

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester Animals Calcium Calcium-Calmodulin-Dependent Protein Kinase Type 2 Calcium Channel Agonists Calcium Channel Blockers Calcium Channels, L-Type Chelating Agents Corpus Striatum Egtazic Acid Enzyme Inhibitors Gene Expression Regulation In Vitro Techniques Male Mice Mice, Inbred C57BL Pyrroles Receptors, Glutamate Signal Transduction Spider Venoms

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