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• W1992096875 startingPage "8282" @default.
• W1992096875 abstract "P-type (Ca V 2.1) Ca 2+ channels are a central conduit of neuronal Ca 2+ entry, so their Ca 2+ feedback regulation promises widespread neurobiological impact. Heterologous expression of recombinant Ca V 2.1 channels demonstrates that the Ca 2+ sensor calmodulin can trigger Ca 2+ -dependent facilitation (CDF) of channel opening. This facilitation occurs when local Ca 2+ influx through individual channels selectively activates the C-terminal lobe of calmodulin. In neurons, however, such calmodulin-mediated processes have yet to be detected, and CDF of native P-type current has thus far appeared different, arguably triggered by other Ca 2+ sensing molecules. Here, in cerebellar Purkinje somata abundant with prototypic P-type channels, we find that the C-terminal lobe of calmodulin does produce CDF, and such facilitation augments Ca 2+ entry during stimulation by repetitive action-potential and complex-spike waveforms. Beyond recapitulating key features of recombinant channels, these neurons exhibit an additional modulatory dimension: developmental upregulation of CDF during postnatal week 2. This phenomenon reflects increasing somatic expression of Ca V 2.1 splice variants that manifest CDF and progressive dendritic targeting of variants lacking CDF. Calmodulin-triggered facilitation is thus fundamental to native Ca V 2.1 and rapidly enhanced during early development." @default.
• W1992096875 created "2016-06-24" @default.
• W1992096875 creator A5009445429 @default.
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• W1992096875 creator A5045973628 @default.
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• W1992096875 date "2005-09-07" @default.
• W1992096875 modified "2023-10-03" @default.
• W1992096875 title "Developmental Activation of Calmodulin-Dependent Facilitation of Cerebellar P-Type Ca²⁺Current" @default.
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• W1992096875 doi "https://doi.org/10.1523/jneurosci.2253-05.2005" @default.
• W1992096875 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/6725527" @default.
• W1992096875 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/16148236" @default.
• W1992096875 hasPublicationYear "2005" @default.
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