ArticleNeuroscience2010
(R)-roscovitine prolongs the mean open time of unitary N-type calcium channel currents.
Article in Neuroscience, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 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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Who cites it
13 citing papers in PubMed, 28 citations in OpenAlex.
- Simulations of active zone structure and function at mammalian NMJs predict that loss of calcium channels alone is not sufficient to replicate LEMS effects.Journal of neurophysiology · 2023Article
- Microphysiological Modeling of the Structure and Function of Neuromuscular Transmitter Release Sites.Frontiers in synaptic neuroscience · 2022Review
- Opposite Roles in Short-Term Plasticity for N-Type and P/Q-Type Voltage-Dependent Calcium Channels in GABAergic Neuronal Connections in the Rat Cerebral Cortex.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2018Article
- New Cav2 calcium channel gating modifiers with agonist activity and therapeutic potential to treat neuromuscular disease.Neuropharmacology · 2018Article
- Lambert-Eaton myasthenic syndrome: mouse passive-transfer model illuminates disease pathology and facilitates testing therapeutic leads.Annals of the New York Academy of Sciences · 2018Review
- Synaptic Pathophysiology and Treatment of Lambert-Eaton Myasthenic Syndrome.Molecular neurobiology · 2015Review
- Cav2.1 channels control multivesicular release by relying on their distance from exocytotic Ca2+ sensors at rat cerebellar granule cells.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2014Article
- Evaluation of a novel calcium channel agonist for therapeutic potential in Lambert-Eaton myasthenic syndrome.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2013Article
- An excess-calcium-binding-site model predicts neurotransmitter release at the neuromuscular junction.Biophysical journal · 2013Article
- Synthesis and biological evaluation of a selective N- and p/q-type calcium channel agonist.ACS medicinal chemistry letters · 2012Article
- Stabilizers of neuronal and mitochondrial calcium cycling as a strategy for developing a medicine for Alzheimer's disease.ACS chemical neuroscience · 2012Review
- Regulation by L-type calcium channels of endocytosis: an overview.Journal of molecular neuroscience : MN · 2012Review
- Domain III regulates N-type (CaV2.2) calcium channel closing kinetics.Journal of neurophysiology · 2012Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
(R)-roscovitine (Ros) is a cyclin-dependent kinase inhibitor that also has been shown to have direct agonist and antagonist actions on Ca(v)2.1 (P/Q-type) and Ca(v) 2.2 (N-type) families of voltage-gated calcium channels. These kinase-independent effects represent a novel opportunity to advance our understanding of calcium channel function and calcium-triggered neurotransmitter release. Furthermore, such actions on calcium channels may direct the development of Ros derivatives as new therapeutic agents. We used patch clamp recordings to characterize mechanisms that underlie the agonist effects of Ros on unitary N-type calcium channel gating. We found that N-type channels normally gate with either a short or long mean open time, that Ros significantly prolonged the mean open time of the long gating component and increased the probability of observing channels that gated with a long open time, but had no effect on single channel conductance. Using Monte Carlo simulations of a single channel kinetic model and Ros interactions, we were able to reproduce our experimental results and investigate the model's microscopic dynamics. In particular, our simulations predicted that the longer open times generated by Ros were due to the appearance of a long open state combined with an increased amount of time spent in transitions between open states. Our results suggest a mechanism for agonist effects of Ros at the level of single channels, and provide a mechanistic explanation for previously reported agonist effects on whole cell calcium currents.
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Identifiers
What OpenQuestion holds
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.