ArticleNeuroscience2002
Calcineurin enhances L-type Ca(2+) channel activity in hippocampal neurons: increased effect with age in culture.
Article in Neuroscience, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
45 citing papers in PubMed, 86 citations in OpenAlex.
- Rapamycin Treatment Reduces Brain Pericyte Constriction in Ischemic Stroke.Translational stroke research · 2025Article
- Calcineurin inhibition may prevent Alzheimer disease in people with Down syndrome.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Review
- Calcium signaling at the interface between astrocytes and brain inflammation.Current opinion in neurobiology · 2025Review
- Variable bioenergetic sensitivity of neurons and astrocytes to insulin and extracellular glucose.npj metabolic health and disease · 2024Article
- Phospholipase D1 Attenuation Therapeutics Promotes Resilience against Synaptotoxicity in 12-Month-Old 3xTg-AD Mouse Model of Progressive Neurodegeneration.International journal of molecular sciences · 2023Article
- The Puzzling Role of Neuron-Specific PMCA Isoforms in the Aging Process.International journal of molecular sciences · 2019Review
- Protective effects of hydroponic Teucrium polium on hippocampal neurodegeneration in ovariectomized rats.BMC complementary and alternative medicine · 2016Article
- A Novel Small Molecule Modulator of Amyloid Pathology.Journal of Alzheimer's disease : JAD · 2016Article
- Navigating Barriers to Vocational Rehabilitation for HIV-Positive Persons.AIDS and behavior · 2016Article
- Calcium-dependent inactivation of calcium channels in the medial striatum increases at eye opening.Journal of neurophysiology · 2015Article
- Intra-CA1 administration of FK-506 (tacrolimus) in rat impairs learning and memory in an inhibitory avoidance paradigm.Iranian journal of basic medical sciences · 2015Article
- FK506-binding protein 1b/12.6: a key to aging-related hippocampal Ca2+ dysregulation?European journal of pharmacology · 2014Review
- Calcineurin and glial signaling: neuroinflammation and beyond.Journal of neuroinflammation · 2014Review
- Article
- Calcineurin-dependent ion channel regulation in heart.Trends in cardiovascular medicine · 2014Review
- Calcium dysregulation and neuroinflammation: discrete and integrated mechanisms for age-related synaptic dysfunction.Ageing research reviews · 2013Review
- Calcineurin signaling mediates activity-dependent relocation of the axon initial segment.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2013Article
- An L-type calcium channel agonist, bay K8644, extends the window of intervention against ischemic neuronal injury.Molecular neurobiology · 2013Article
- Hypoxia enhances high-voltage-activated calcium currents in rat primary cortical neurons via calcineurin.Epilepsy research · 2012Article
- Reduction in neuronal L-type calcium channel activity in a double knock-in mouse model of Alzheimer's disease.Biochimica et biophysica acta · 2012Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
The Ca(2+)/calmodulin-dependent protein phosphatase, calcineurin, modulates a number of key Ca(2+) signaling pathways in neurons, and has been implicated in Ca(2+)-dependent negative feedback inactivation of N-methyl-D-aspartate receptors and voltage-sensitive Ca(2+) channels. In contrast, we report here that three mechanistically disparate calcineurin inhibitors, FK-506, cyclosporin A, and the calcineurin autoinhibitory peptide, inhibited high-voltage-activated Ca(2+) channel currents by up to 40% in cultured hippocampal neurons, suggesting that calcineurin acts to enhance Ca(2+) currents. This effect occurred with Ba(2+) or Ca(2+) as charge carrier, and with or without intracellular Ca(2+) buffered by EGTA. Ca(2+)-dependent inactivation of Ca(2+) channels was not affected by FK-506. The immunosuppressant, rapamycin, and the protein phosphatase 1/2A inhibitor, okadaic acid, did not decrease Ca(2+) channel current, showing specificity for effects on calcineurin. Blockade of L-type Ca(2+) channels with nimodipine fully negated the effect of FK-506 on Ca(2+) channel current, while blockade of N-, and P-/Q-type Ca(2+) channels enhanced FK-506-mediated inhibition of the remaining L-type-enriched current. FK-506 also inhibited substantially more Ca(2+) channel current in 4-week-old vs. 2-week-old cultures, an effect paralleled by an increase in calcineurin A mRNA levels. These studies provide the first evidence that calcineurin selectively enhances L-type Ca(2+) channel activity in neurons. Moreover, this action appears to be increased concomitantly with the well-characterized increase in L-type Ca(2+) channel availability in hippocampal neurons with age-in-culture.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.