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PMID: 11865310 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Differential modulation of Ca(v)2.1 channels by calmodulin and Ca2+-binding protein 1.

Nature neuroscience ·Vol. 5 ·No. 3 ·2002-03-00 ·Pages 210-7

Lee A, Westenbroek RE, Haeseleer F, Palczewski K, Scheuer T, Catterall WA

Abstract

Ca(v)2.1 channels, which mediate P/Q-type Ca2+ currents, undergo Ca2+/calmodulin (CaM)-dependent inactivation and facilitation that can significantly alter synaptic efficacy. Here we report that the neuronal Ca2+-binding protein 1 (CaBP1) modulates Ca(v)2.1 channels in a manner that is markedly different from modulation by CaM. CaBP1 enhances inactivation, causes a depolarizing shift in the voltage dependence of activation, and does not support Ca2+-dependent facilitation of Ca(v)2.1 channels. These inhibitory effects of CaBP1 do not require Ca2+, but depend on the CaM-binding domain in the alpha1 subunit of Ca(v)2.1 channels (alpha12.1). CaBP1 binds to the CaM-binding domain, co-immunoprecipitates with alpha12.1 from transfected cells and brain extracts, and colocalizes with alpha12.1 in discrete microdomains of neurons in the hippocampus and cerebellum. Our results identify an interaction between Ca2+ channels and CaBP1 that may regulate Ca2+-dependent forms of synaptic plasticity by inhibiting Ca2+ influx into neurons.

MeSH Terms
Animals Brain/cytology,metabolism Calcium/metabolism Calcium Channels, N-Type/metabolism Calcium-Binding Proteins/metabolism Calmodulin/metabolism Cell Line Cerebellum/cytology,metabolism Chelating Agents/pharmacology Egtazic Acid/analogs & derivatives,pharmacology Hippocampus/cytology,metabolism Humans Male Models, Molecular Neurons/drug effects,metabolism Patch-Clamp Techniques Protein Binding Protein Structure, Secondary Protein Subunits Protozoan Proteins/metabolism Rats Rats, Sprague-Dawley Two-Hybrid System Techniques
Chemicals
Calcium Channels, N-Type Calcium-Binding Proteins Calmodulin Chelating Agents Protein Subunits Protozoan Proteins calcium-binding protein 1, Dictyostelium discoideum voltage-dependent calcium channel (P-Q type) Egtazic Acid Calcium
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Lee Amy
Department of Pharmacology, University of Washington School of Medicine, Seattle, Washington 98195-7280, USA.
Westenbroek Ruth E
Haeseleer Françoise
Palczewski Krzysztof
Scheuer Todd
Catterall William A
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Article Info
Journal
Nature neuroscience
Abbr.
Nat Neurosci
ISSN
1097-6256
DOI
10.1038/nn805
Published
2002-03-00
Pages
210-7
Language
English
Region
United States
NLM ID
9809671
PMCID
PMC1435861
Subset
IM
Grants
NEI NIH HHS · R01 EY08061 · United States
NINDS NIH HHS · F32 NS010645 · United States
NINDS NIH HHS · R01 NS22625 · United States
NEI NIH HHS · R01 EY008061 · United States
NINDS NIH HHS · F32 NS10645 · United States
NINDS NIH HHS · R01 NS022625 · United States
External Links
PubMed source DOI: 10.1038/nn805 PMC Full Text View journal details
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