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Title: Developmental activation of calmodulin-dependent facilitation of cerebellar P-type Ca2+current
Authors: Chaudhuri, D.
Yue, D.T.
Alseikhan, B.A.
Chang, S.Y. 
Soong, T.W. 
Keywords: α1A
Alternative splicing
Cerebellar Purkinje neuron
EF hand
P/Q-type channel
Short-term synaptic plasticity
Issue Date: 2005
Citation: Chaudhuri, D., Yue, D.T., Alseikhan, B.A., Chang, S.Y., Soong, T.W. (2005). Developmental activation of calmodulin-dependent facilitation of cerebellar P-type Ca2+current. Journal of Neuroscience 25 (36) : 8282-8294. ScholarBank@NUS Repository.
Abstract: P-type (Cav2.1) Ca2+ channels are a central conduit of neuronal Ca2+ entry, so their Ca2+ feedback regulation promises widespread neurobiological impact. Heterologous expression of recombinant Cav2.1 channels demonstrates that the Ca2+ sensor calmodulin can trigger Ca2+-dependent facilitation (CDF) of channel opening. This facilitation occurs when local Ca2+ 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 Ca2+ 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 Ca2+ 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 Cav2.1 splice variants that manifest CDF and progressive dendritic targeting of variants lacking CDF. Calmodulin-triggered facilitation is thus fundamental to native Ca v2.1 and rapidly enhanced during early development. Copyright © 2005 Society for Neuroscience.
Source Title: Journal of Neuroscience
ISSN: 02706474
DOI: 10.1523/JNEUROSCI.2253-05.2005
Appears in Collections:Staff Publications

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