ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2014
Synaptic gain-of-function effects of mutant Cav2.1 channels in a mouse model of familial hemiplegic migraine are due to increased basal [Ca2+]i.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 53 citations in OpenAlex.
- Hemiplegic migraine: genetics and pathophysiology.The Journal of clinical investigation · 2026Review
- Human neuronal networks on micro-electrode arrays as a tool to assess genotype-phenotype correlation in CACNA1A-related disorders.Stem cell reports · 2026Article
- CACNA1A loss-of-function affects neurogenesis in human iPSC-derived neural models.Cellular and molecular life sciences : CMLS · 2025Article
- Mechanisms underlying CSD initiation implicated by genetic mouse models of migraine.The journal of headache and pain · 2025Review
- Voltage-gated calcium channels in genetic epilepsies.Journal of neurochemistry · 2024Review
- A structural analysis of the splice-specific functional impact of the pathogenic familial hemiplegic migraine type 1 S218L mutation on CaMolecular brain · 2024Article
- Presynaptic neurons self-tune by inversely coupling neurotransmitter release with the abundance of CaV2 voltage-gated CaProceedings of the National Academy of Sciences of the United States of America · 2024Article
- Models of Trigeminal Activation: Is There an Animal Model of Migraine?Brain sciences · 2024Review
- Chronic pregabalin treatment protects against spreading depolarization and alters hippocampal synaptic characteristics in a model of familial hemiplegic migraine-type 1.Molecular brain · 2023Article
- The NMDA receptor antagonists memantine and ketamine as anti-migraine agents.Naunyn-Schmiedeberg's archives of pharmacology · 2023Review
- Astrocytic Glutamate Transporters and Migraine.Neurochemical research · 2023Review
- Regulation of Presynaptic Calcium Channels.Advances in neurobiology · 2023Article
- Hyperexcitable superior colliculus and fatal brainstem spreading depolarization in a model of Sudden Unexpected Death in Epilepsy.Brain communications · 2022Article
- Simultaneous administration of cocaine and caffeine dysregulates HCN and T-type channels.Psychopharmacology · 2021Article
- Rare CACNA1A mutations leading to congenital ataxia.Pflugers Archiv : European journal of physiology · 2020Review
- Presynaptic development is controlled by the core active zone proteins CAST/ELKS.The Journal of physiology · 2020Article
- Presynaptic calcium channels: specialized control of synaptic neurotransmitter release.Nature reviews. Neuroscience · 2020Review
- Genetic mouse models of migraine.The journal of headache and pain · 2019Review
- The Role of CaCell reports · 2019Article
- Zebrafish as a Model System for the Study of Severe CaFrontiers in molecular neuroscience · 2019Review
Corrections and comments
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Authors and funding
8 authors at 5 institutions in 3 countries.
Funding
Abstract
Specific missense mutations in the CACNA1A gene, which encodes a subunit of voltage-gated CaV2.1 channels, are associated with familial hemiplegic migraine type 1 (FHM1), a rare monogenic subtype of common migraine with aura. We used transgenic knock-in (KI) mice harboring the human pathogenic FHM1 mutation S218L to study presynaptic Ca(2+) currents, EPSCs, and in vivo activity at the calyx of Held synapse. Whole-cell patch-clamp recordings of presynaptic terminals from S218L KI mice showed a strong shift of the calcium current I-V curve to more negative potentials, leading to an increase in basal [Ca(2+)]i, increased levels of spontaneous transmitter release, faster recovery from synaptic depression, and enhanced synaptic strength despite smaller action-potential-elicited Ca(2+) currents. The gain-of-function of transmitter release of the S218L mutant was reproduced in vivo, including evidence for an increased release probability, demonstrating its relevance for glutamatergic transmission. This synaptic phenotype may explain the misbalance between excitation and inhibition in neuronal circuits resulting in a persistent hyperexcitability state and other migraine-relevant mechanisms such as an increased susceptibility to cortical spreading depression.
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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.