Excitation–transcription coupling in sympathetic neurons and the molecular mechanism of its initiation
Open accessAbstract
In excitable cells, membrane depolarization and activation of voltage-gated Ca²+ (Ca(V)) channels trigger numerous cellular responses, including muscle contraction, secretion, and gene expression. Yet, while the mechanisms underlying excitation-contraction and excitation-secretion coupling have been extensively characterized, how neuronal activity is coupled to gene expression has remained more elusive. In this article, we will discuss recent progress toward understanding the relationship between patterns of channel activity driven by membrane depolarization and activation of the nuclear transcription factor CREB. We show that signaling strength is steeply dependent on membrane depolarization and is more sensitive to the open probability of Ca(V) channels than the Ca²+ entry itself. Furthermore, our data indicate that by decoding Ca(V) channel activity, CaMKII (a Ca²+/calmodulin-dependent protein kinase) links membrane excitation to activation of CREB in the nucleus. Together, these results revealed some interesting and unexpected similarities between excitation-transcription coupling and other forms of excitation-response coupling.
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The Guenthner study used a genetic labeling technique nearly identical to ours, but recombination was driven by promoters for immediate-early genes Fos and Arc, upregulated as part of excitation-transcription neuronal response to synaptic activity initiated by CREB phosphorylation.
“The Guenthner study [9] used a genetic labeling technique nearly identical to ours, but recombination was driven by promoters for the immediate-early genes Fos and Arc, upregulated as part of the “excitation-transcription” neuronal response to synaptic activity initiated by CREB phosphorylation [40].”
From Tamoxifen induces cellular stress in the nervous system by inhibiting cholesterol synthesis (2015) · cites this paper as [40]
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- Authors
- Ma, H., Groth, R. D., Wheeler, D. G., Barrett, C. F., & Tsien, R. W.
- Affiliations
- Stanford Medicine (US)
- Corresponding author
- Tsien, Richard W.
- Venue
- Neuroscience Research
- Publisher
- Elsevier BV
- Published
- 2011-05
- Volume
- 70
- Issue
- 1
- Pages
- 2-8
- ISSN
- 0168-0102 (ISSN-L)
- PMC
- PMC3930329
- OpenAlex
- W1987938334
- Cited by
- 42
- References
- 48
- Citations by year
- 2025: 3 · 2024: 2 · 2023: 1 · 2021: 2 · 2020: 2 · 2019: 3 · 2018: 3 · 2017: 10 · 2016: 1 · 2015: 7 · 2014: 2 · 2013: 2 · 2012: 3
- FWCI
- 0.23
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Neuroscience Research (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of General Medical Sciences
- National Institute of Neurological Disorders and Stroke
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion channel regulation and function
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Keywords
- excitation-transcription coupling, sympathetic neurons, voltage-gated calcium channels, CREB, CaMKII, membrane depolarization, calcium signaling, gene expression
- MeSH terms
- Action Potentials, Animals, Ganglia, Sympathetic, Humans, Neurons, Calcium Channels, Calcium Signaling
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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