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A mechanism for the direct regulation of T-type calcium channels by Ca2+/calmodulin-dependent kinase II.

Philip J Welsby, Hongge Wang, Joshua T Wolfe, Roger J Colbran, Michael L Johnson, Paula Q Barrett

J. Neurosci., 2003 Nov 5 , 23, 10116-21

Low-voltage-activated (LVA) Ca2+ channels are widely distributed throughout the CNS and are important determinants of neuronal excitability, initiating dendritic and somatic Ca2+ spikes that trigger and shape the pattern of action potential firing. Here, we define a molecular mechanism underlying the dynamic regulation of alpha1H channels (Cav3.2), by Ca2+/CaM-dependent protein kinase II (CaMKII). We show that channel regulation is selective for the LVA alpha1H Ca2+ channel subtype, depends on determinants in the alpha1H II-III intracellular loop, and requires the phosphorylation of a serine residue absent from unregulated alpha1G (Cav3.1) channels. These studies identify the alpha1H channel as a new substrate for CaMKII and provide the first molecular mechanism for the direct regulation of T-type Ca2+ channels by a protein kinase. Our data suggest a novel mechanism for modulating the integrative properties of neurons.

http://www.ncbi.nlm.nih.gov/pubmed/14602827