ArticleBritish journal of pharmacology2007
Roscovitine, a cyclin-dependent kinase inhibitor, affects several gating mechanisms to inhibit cardiac L-type (Ca(V)1.2) calcium channels.
Article in British journal of pharmacology, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 48 citations in OpenAlex.
- Inactivation of CaV1 and CaV2 channels.The Journal of general physiology · 2025Review
- CACNA1C-Related Channelopathies.Handbook of experimental pharmacology · 2023Review
- Impaired CaJournal of molecular and cellular cardiology · 2022Article
- A Review on Mechanistic Insight of Plant Derived Anticancer Bioactive Phytocompounds and Their Structure Activity Relationship.Molecules (Basel, Switzerland) · 2022Review
- Small Molecules as Modulators of Voltage-Gated Calcium Channels in Neurological Disorders: State of the Art and Perspectives.Molecules (Basel, Switzerland) · 2022Review
- Suppression of ventricular arrhythmias by targeting late L-type Ca2+ current.The Journal of general physiology · 2021Article
- L-type channel inactivation balances the increased peak calcium current due to absence of Rad in cardiomyocytes.The Journal of general physiology · 2021Article
- LCM and RNA-seq analyses revealed roles of cell cycle and translational regulation and homoeolog expression bias in cotton fiber cell initiation.BMC genomics · 2021Article
- Drug Development and the Use of Induced Pluripotent Stem Cell-Derived Cardiomyocytes for Disease Modeling and Drug Toxicity Screening.International journal of molecular sciences · 2020Review
- Dysfunctional Cav1.2 channel in Timothy syndrome, from cell to bedside.Experimental biology and medicine (Maywood, N.J.) · 2019Article
- A mutation in CaThe Journal of general physiology · 2019Article
- Anticancer Activity of Natural Compounds from Plant and Marine Environment.International journal of molecular sciences · 2018Review
- Substrates and potential therapeutics of ventricular arrhythmias in heart failure.European journal of pharmacology · 2018Review
- Wanted: Class VI Antiarrhythmic Drug Action; New Start for a Rational Drug Therapy.Journal of heart health · 2018Article
- Mutations in voltage-gated L-type calcium channel: implications in cardiac arrhythmia.Channels (Austin, Tex.) · 2018Review
- Inhibition of CDK5 Alleviates the Cardiac Phenotypes in Timothy Syndrome.Stem cell reports · 2017Article
- Article
- Enhanced Late Na and Ca Currents as Effective Antiarrhythmic Drug Targets.Frontiers in pharmacology · 2017Review
- Calcium Revisited: New Insights Into the Molecular Basis of Long-QT Syndrome.Circulation. Arrhythmia and electrophysiology · 2016Review
- Rational strategy to stop arrhythmias: Early afterdepolarizations and L-type Ca2+ current.The Journal of general physiology · 2015Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
background and purposeL-type calcium channels (Ca((V))1.2) play an important role in cardiac contraction. Roscovitine, a cyclin-dependent kinase inhibitor and promising anticancer drug, has been shown to affect Ca((V))1.2 by inhibiting current amplitude and slowing activation. This research investigates the mechanism by which roscovitine inhibits Ca((V))1.2 channels. EXPERIMENTAL APPROACH: Ca((V))1.2 channels were transfected into HEK 293 cells, using the calcium phosphate precipitation method, and currents were measured using the whole-cell patch clamp technique. KEY
resultsRoscovitine slows activation at all voltages, which precludes one previously proposed mechanism. In addition, roscovitine enhances voltage-dependent, but not calcium-dependent inactivation. This enhancement resulted from both an acceleration of inactivation and a slowing of the recovery from inactivation. Internally applied roscovitine failed to affect Ca((V))1.2 currents, which supports a kinase-independent mechanism and extracellular binding site. Unlike the dihydropyridines, closed state inactivation was not affected by roscovitine. Inactivation was enhanced in a dose-dependent manner with an IC(50)=29.5+/-12 microM, which is close to that for slow activation and inhibition. CONCLUSIONS AND IMPLICATIONS: We conclude that roscovitine binds to an extracellular site on Ca((V))1.2 channels to inhibit current by both slowing activation and enhancing inactivation. Purine-based drugs could become a new option for treatment of diseases that benefit from L-channel inhibition such as cardiac arrhythmias and hypertension.
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