CaV1.2 and CaV1.3 neuronal L-type calcium channels: Differential targeting and signaling to pCREB

Hua Zhang, Yu Fu, Christophe Altier, Josef Platzer, D. James Surmeier, Ilya Bezprozvanny*

*Corresponding author for this work

Research output: Contribution to journalArticle

78 Scopus citations

Abstract

Neurons express multiple types of voltage-gated calcium (Ca2+) channels. Two subtypes of neuronal L-type Ca2+ channels are encoded by CaV1.2 and CaV1.3 pore-forming subunits. To compare targeting of CaV1.2 and CaV1.3 L-type Ca2+ channels, we transfected rat hippocampal neuronal cultures with surface-epitope-tagged sHA-CaV1.2 or sHA-CaV1.3a constructs and found that: (i) both sHA-CaV1.2 and sHA-Ca V1.3a form clusters on the neuronal plasma membrane surface; (ii) when compared with sHA-CaV1.2 surface clusters, the sHA-Ca V1.3a surface clusters were 10% larger and 25% brighter, but 35% less abundant; (iii) 81% of sHA-CaV1.2 surface clusters, but only 48% of sHA-CaV1.3a surface clusters, co-localized with synapsin clusters; (iv) co-expression with GFP-Shank-1B had no significant effect on sHA-Ca V1.2 surface clusters, but promoted formation and synaptic localization of sHA-CaV1.3a surface clusters. In experiments with dihydropyridine-resistant CaV1.2 and CaV1.3a mutants we demonstrated that CaV1.3a L-type Ca2+ channels preferentially mediate nuclear pCREB signaling in hippocampal neurons at low, but not at high, levels of stimulation. In experiments with primary neuronal cultures from CaV1.3 knockout mice we discovered that Ca V1.3 channels play a more important role in pCREB signaling in striatal medium spiny neurons than in hippocampal neurons. Our results provide novel insights into the function of CaV1.2 and CaV1.3 L-type Ca2+ channels in the brain.

Original languageEnglish (US)
Pages (from-to)2297-2310
Number of pages14
JournalEuropean Journal of Neuroscience
Volume23
Issue number9
DOIs
StatePublished - May 2006

Keywords

  • CREB
  • Calcium channels
  • Postsynaptic density
  • Synapse
  • Synaptic plasticity

ASJC Scopus subject areas

  • Neuroscience(all)

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