ArticleThe Journal of general physiology2009
The Ca2+ channel beta subunit determines whether stimulation of Gq-coupled receptors enhances or inhibits N current.
Article in The Journal of general physiology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 40 citations in OpenAlex.
- Article
- Molecular basis of the PIPeLife · 2022Article
- Modality specific roles for metabotropic GABAergic signaling and calcium induced calcium release mechanisms in regulating cold nociception.Frontiers in molecular neuroscience · 2022Article
- Regulatory effects of protein S-acylation on insulin secretion and insulin action.Open biology · 2021Review
- Article
- Article
- Actions and Mechanisms of Polyunsaturated Fatty Acids on Voltage-Gated Ion Channels.Frontiers in physiology · 2017Review
- Gα14 subunit-mediated inhibition of voltage-gated Ca2+ and K+ channels via neurokinin-1 receptors in rat celiac-superior mesenteric ganglion neurons.Journal of neurophysiology · 2016Article
- Differential interaction of β2e with phosphoinositides: A comparative study between β2e and MARCKS.Channels (Austin, Tex.) · 2016Article
- Suppression of agrin-22 production and synaptic dysfunction in Cln1 (-/-) mice.Annals of clinical and translational neurology · 2015Article
- The Physiology, Pathology, and Pharmacology of Voltage-Gated Calcium Channels and Their Future Therapeutic Potential.Pharmacological reviews · 2015Review
- Molecular Basis of the Membrane Interaction of the β2e Subunit of Voltage-Gated Ca(2+) Channels.Biophysical journal · 2015Article
- Constitutive and ghrelin-dependent GHSR1a activation impairs CaV2.1 and CaV2.2 currents in hypothalamic neurons.The Journal of general physiology · 2015Article
- Dynamic phospholipid interaction of β2e subunit regulates the gating of voltage-gated Ca2+ channels.The Journal of general physiology · 2015Article
- Phosphoinositides regulate ion channels.Biochimica et biophysica acta · 2015Review
- Voltage-dependent regulation of CaV2.2 channels by Gq-coupled receptor is facilitated by membrane-localized β subunit.The Journal of general physiology · 2014Article
- Ion channel regulation by protein S-acylation.The Journal of general physiology · 2014Review
- L-type CaWiley interdisciplinary reviews. Membrane transport and signaling · 2014Article
- Regulation of Ca(V)2 calcium channels by G protein coupled receptors.Biochimica et biophysica acta · 2013Review
- Structure and function of the β subunit of voltage-gated Ca²⁺ channels.Biochimica et biophysica acta · 2013Review
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
In superior cervical ganglion (SCG) neurons, stimulation of M(1) receptors (M(1)Rs) produces a distinct pattern of modulation of N-type calcium (N-) channel activity, enhancing currents elicited with negative test potentials and inhibiting currents elicited with positive test potentials. Exogenously applied arachidonic acid (AA) reproduces this profile of modulation, suggesting AA functions as a downstream messenger of M(1)Rs. In addition, techniques that diminish AA's concentration during M(1)R stimulation minimize N-current modulation. However, other studies suggest depletion of phosphatidylinositol-4,5-bisphosphate during M(1)R stimulation suffices to elicit modulation. In this study, we used an expression system to examine the physiological mechanisms regulating modulation. We found the beta subunit (Ca(V)beta) acts as a molecular switch regulating whether modulation results in enhancement or inhibition. In human embryonic kidney 293 cells, stimulation of M(1)Rs or neurokinin-1 receptors (NK-1Rs) inhibited activity of N channels formed by Ca(V)2.2 and coexpressed with Ca(V)beta1b, Ca(V)beta3, or Ca(V)beta4 but enhanced activity of N channels containing Ca(V)beta2a. Exogenously applied AA produced the same pattern of modulation. Coexpression of Ca(V)beta2a, Ca(V)beta3, and Ca(V)beta4 recapitulated the modulatory response previously seen in SCG neurons, implying heterogeneous association of Ca(V)beta with Ca(V)2.2. Further experiments with mutated, chimeric Ca(V)beta subunits and free palmitic acid revealed that palmitoylation of Ca(V)beta2a is essential for loss of inhibition. The data presented here fit a model in which Ca(V)beta2a blocks inhibition, thus unmasking enhancement. Our discovery that the presence or absence of palmitoylated Ca(V)beta2a toggles M(1)R- or NK-1R-mediated modulation of N current between enhancement and inhibition identifies a novel role for palmitoylation. Moreover, these findings predict that at synapses, modulation of N-channel activity by M(1)Rs or NK-1Rs will fluctuate between enhancement and inhibition based on the presence of palmitoylated Ca(V)beta2a.
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