ArticleThe Journal of clinical investigation2004
Isoform-specific regulation of mood behavior and pancreatic beta cell and cardiovascular function by L-type Ca 2+ channels.
Article in The Journal of clinical investigation, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 109 papers.
What it found
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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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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
109 citing papers in PubMed, 208 citations in OpenAlex.
- Inhibition of CaV1.4 channels by CaV3 channel antagonists ML218 and Z944.The Journal of general physiology · 2026Article
- L-Type CaCirculation research · 2026Article
- Stimulation of CaScience signaling · 2025Article
- L-type calcium channel blockade worsens glucose tolerance and β-cell function in C57BL6/J mice exposed to intermittent hypoxia.American journal of physiology. Endocrinology and metabolism · 2025Article
- Cardiac injury caused by iron overload in thalassemia.Frontiers in pediatrics · 2025Review
- Neuroprotective actions of norepinephrine in neurological diseases.Pflugers Archiv : European journal of physiology · 2024Review
- Selective blockade of CaNature communications · 2024Article
- A biophysical minimal model to investigate age-related changes in CA1 pyramidal cell electrical activity.PloS one · 2024Article
- The human channel gating-modifying A749G CACNA1D (Cav1.3) variant induces a neurodevelopmental syndrome-like phenotype in mice.JCI insight · 2023Article
- New Insights into the Nephroprotective Potential of Lercanidipine.International journal of molecular sciences · 2023Review
- Regulation of the CaThe Journal of neuroscience : the official journal of the Society for Neuroscience · 2023Article
- αeLife · 2023Article
- CaBritish journal of pharmacology · 2023Review
- CaNeuropharmacology · 2023Article
- Mechanisms and physiological implications of cooperative gating of clustered ion channels.Physiological reviews · 2022Review
- CaScience advances · 2022Article
- L-Type CaCells · 2022Article
- Enhanced long-term potentiation and impaired learning in mice lacking alternative exon 33 of CaTranslational psychiatry · 2022Article
- Propagation of Pacemaker Activity and Peristaltic Contractions in the Mouse Renal Pelvis Rely on CaFunction (Oxford, England) · 2022Article
- Beta-Cell Ion Channels and Their Role in Regulating Insulin Secretion.Comprehensive Physiology · 2021Review
49 more citing papers are in PubMed but not listed here.
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Authors and funding
16 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Ca(v)1.2 and Ca(v)1.3 L-type Ca(2+) channels (LTCCs) are believed to underlie Ca(2+) currents in brain, pancreatic beta cells, and the cardiovascular system. In the CNS, neuronal LTCCs control excitation-transcription coupling and neuronal plasticity. However, the pharmacotherapeutic implications of CNS LTCC modulation are difficult to study because LTCC modulators cause cardiovascular (activators and blockers) and neurotoxic (activators) effects. We selectively eliminated high dihydropyridine (DHP) sensitivity from Ca(v)1.2 alpha 1 subunits (Ca(v)1.2DHP-/-) without affecting function and expression. This allowed separation of the DHP effects of Ca(v)1.2 from those of Ca(v)1.3 and other LTCCs. DHP effects on pancreatic beta cell LTCC currents, insulin secretion, cardiac inotropy, and arterial smooth muscle contractility were lost in Ca(v)1.2DHP-/- mice, which rules out a direct role of Ca(v)1.3 for these physiological processes. Using Ca(v)1.2DHP-/- mice, we established DHPs as mood-modifying agents: LTCC activator-induced neurotoxicity was abolished and disclosed a depression-like behavioral effect without affecting spontaneous locomotor activity. LTCC activator BayK 8644 (BayK) activated only a specific set of brain areas. In the ventral striatum, BayK-induced release of glutamate and 5-HT, but not dopamine and noradrenaline, was abolished. This animal model provides a useful tool to elucidate whether Ca(v)1.3-selective channel modulation represents a novel pharmacological approach to modify CNS function without major peripheral effects.
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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.