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

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Citation

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

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

Nat Neurosci. 2002 Mar;5(3):210-7.

PubMed ID
11865310 [ View in PubMed
]
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.

DrugBank Data that Cites this Article

Polypeptides
NameUniProt ID
Voltage-dependent P/Q-type calcium channel subunit alpha-1AO00555Details