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Ca V 1.2 and Ca V 1.3 neuronal L‐type calcium channels: differential targeting and signaling to pCREB
Author(s) -
Zhang Hua,
Fu Yu,
Altier Christophe,
Platzer Josef,
Surmeier D. James,
Bezprozvanny Ilya
Publication year - 2006
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/j.1460-9568.2006.04734.x
Subject(s) - chemistry , voltage dependent calcium channel , hippocampal formation , calcium , r type calcium channel , biophysics , calcium signaling , t type calcium channel , biology , neuroscience , organic chemistry
Neurons express multiple types of voltage‐gated calcium (Ca 2+ ) channels. Two subtypes of neuronal L‐type Ca 2+ channels are encoded by Ca V 1.2 and Ca V 1.3 pore‐forming subunits. To compare targeting of Ca V 1.2 and Ca V 1.3 L ‐type Ca 2+ channels, we transfected rat hippocampal neuronal cultures with surface‐epitope‐tagged sHA‐Ca V 1.2 or sHA‐Ca V 1.3a constructs and found that: (i) both sHA‐Ca V 1.2 and sHA‐Ca V 1.3a form clusters on the neuronal plasma membrane surface; (ii) when compared with sHA‐Ca V 1.2 surface clusters, the sHA‐Ca V 1.3a surface clusters were 10% larger and 25% brighter, but 35% less abundant; (iii) 81% of sHA‐Ca V 1.2 surface clusters, but only 48% of sHA‐Ca V 1.3a surface clusters, co‐localized with synapsin clusters; (iv) co‐expression with GFP‐Shank‐1B had no significant effect on sHA‐Ca V 1.2 surface clusters, but promoted formation and synaptic localization of sHA‐Ca V 1.3a surface clusters. In experiments with dihydropyridine‐resistant Ca V 1.2 and Ca V 1.3a mutants we demonstrated that Ca V 1.3a L‐type Ca 2+ 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 Ca V 1.3 knockout mice we discovered that Ca V 1.3 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 Ca V 1.2 and Ca V 1.3 L ‐type Ca 2+ channels in the brain.