Referenced in: none

Automatically associated channels: Cav2.1

Title: Developmental activation of calmodulin-dependent facilitation of cerebellar P-type Ca2+ current.

Authors: Dipayan Chaudhuri, Badr A Alseikhan, Siao Yun Chang, Tuck Wah Soong, David T Yue

Journal, date & volume: J. Neurosci., 2005 Sep 7 , 25, 8282-94

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/16148236

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 CaV2.1 and rapidly enhanced during early development.