ArticleProceedings of the National Academy of Sciences of the United States of America2004
Cavbeta-subunit displacement is a key step to induce the reluctant state of P/Q calcium channels by direct G protein regulation.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 35 citations in OpenAlex.
- Mechanotransduction-Driven Modulation ofInternational journal of molecular sciences · 2025Article
- Opioid Receptor Regulation of Neuronal Voltage-Gated Calcium Channels.Cellular and molecular neurobiology · 2021Review
- Review: CaThe open neurology journal · 2016Article
- Cacnb4 directly couples electrical activity to gene expression, a process defective in juvenile epilepsy.The EMBO journal · 2012Article
- The ß subunit of voltage-gated Ca2+ channels.Physiological reviews · 2010Review
- Determinants of the voltage dependence of G protein modulation within calcium channel beta subunits.Pflugers Archiv : European journal of physiology · 2009Article
- Mutations of nonconserved residues within the calcium channel alpha1-interaction domain inhibit beta-subunit potentiation.The Journal of general physiology · 2008Article
- Orientation of the calcium channel beta relative to the alpha(1)2.2 subunit is critical for its regulation of channel activity.PloS one · 2008Article
- The importance of occupancy rather than affinity of CaV(beta) subunits for the calcium channel I-II linker in relation to calcium channel function.The Journal of physiology · 2006Article
- Interaction via a key tryptophan in the I-II linker of N-type calcium channels is required for beta1 but not for palmitoylated beta2, implicating an additional binding site in the regulation of channel voltage-dependent properties.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2005Article
- Tetanic depression is overcome by tonic adenosine A(2A) receptor facilitation of L-type Ca(2+) influx into rat motor nerve terminals.The Journal of physiology · 2004Article
- Nuclear life of the voltage-gated Cacnb4 subunit and its role in gene transcription regulation.Channels (Austin, Tex.)Article
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
P/Q Ca(2+) channel activity is inhibited by G protein-coupled receptor activation. Channel inhibition requires a direct Gbetagamma binding onto the pore-forming subunit, Ca(v)2.1. It is characterized by biophysical changes, including current amplitude reduction, activation kinetic slowing, and an I-V curve shift, which leads to a reluctant mode. Here, we have characterized the contribution of the auxiliary beta(3)-subunit to channel regulation by G proteins. The shift in I-V to a P/Q reluctant mode is exclusively observed in the presence of beta(3). Along with the observation that Gbetagamma has no effect on the I-V curve of Ca(v)2.1 alone, we propose that the reluctant mode promoted by Gbetagamma corresponds to a state in which the beta(3)-subunit has been displaced from its channel-binding site. We validate this hypothesis with a beta(3)-I-II(2.1) loop chimera construct. Gbetagamma binding onto the I-II(2.1) loop portion of the chimera releases the beta(3)-binding domain and makes it available for binding onto the I-II loop of Ca(v)1.2, a G protein-insensitive channel. This finding is extended to the full-length Ca(v)2.1 channel by using fluorescence resonance energy transfer. Gbetagamma injection into Xenopus oocytes displaces a Cy3-labeled beta(3)-subunit from a GFP-tagged Ca(v)2.1 channel. We conclude that beta-subunit dissociation from the channel complex constitutes a key step in P/Q calcium channel regulation by G proteins that underlies the reluctant state and is an important process for modulating neurotransmission through G protein-coupled receptors.
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