ArticleThe Journal of physiology2003
The familial hemiplegic migraine mutation R192Q reduces G-protein-mediated inhibition of P/Q-type (Ca(V)2.1) calcium channels expressed in human embryonic kidney cells.
Article in The Journal of physiology, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 61 citations in OpenAlex.
- Hemiplegic migraine: genetics and pathophysiology.The Journal of clinical investigation · 2026Review
- fMRI Insights into Visual Cortex Dysfunction as a Biomarker for Migraine with Aura.Neurology international · 2025Review
- Calcium Ions in the Physiology and Pathology of the Central Nervous System.International journal of molecular sciences · 2024Review
- Voltage-dependent G-protein regulation of CaScience advances · 2024Article
- A Review of theDiseases (Basel, Switzerland) · 2024Review
- Functional Characterization of Four Known Cav2.1 Variants Associated with Neurodevelopmental Disorders.Membranes · 2023Article
- The complexities of CACNA1A in clinical neurogenetics.Journal of neurology · 2022Article
- Opioid Receptor Regulation of Neuronal Voltage-Gated Calcium Channels.Cellular and molecular neurobiology · 2021Review
- Migraine: Calcium Channels and Glia.International journal of molecular sciences · 2021Review
- Quantitative genome-wide association study of six phenotypic subdomains identifies novel genome-wide significant variants in autism spectrum disorder.Translational psychiatry · 2020Article
- Rare CACNA1A mutations leading to congenital ataxia.Pflugers Archiv : European journal of physiology · 2020Review
- Zebrafish as a Model System for the Study of Severe CaFrontiers in molecular neuroscience · 2019Review
- Calcium channel gating.Pflugers Archiv : European journal of physiology · 2018Review
- Calcium channels and synaptic transmission in familial hemiplegic migraine type 1 animal models.Biophysical reviews · 2014Review
- The E1015K variant in the synprint region of the CaV2.1 channel alters channel function and is associated with different migraine phenotypes.The Journal of biological chemistry · 2013Article
- Regulation of Ca(V)2 calcium channels by G protein coupled receptors.Biochimica et biophysica acta · 2013Review
- Article
- Rim1 modulates direct G-protein regulation of Ca(v)2.2 channels.Pflugers Archiv : European journal of physiology · 2011Article
- CaV2.1 channelopathies.Pflugers Archiv : European journal of physiology · 2010Review
- Insights into migraine mechanisms and CaV2.1 calcium channel function from mouse models of familial hemiplegic migraine.The Journal of physiology · 2010Review
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Authors and funding
3 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Familial hemiplegic migraine is associated with at least 13 different missense mutations in the alpha1A Ca(2+) channel subunit. Some of these mutations have been shown to affect the biophysical properties of alpha1A currents. To date, no study has examined the influence of such mutations on the G-protein regulation of channel function. Because G-proteins inhibit movement of the voltage sensor, we examined the effects of the R192Q mutation, which neutralizes a positive charge in the first S4 segment. Human wild-type (WT) or R192Q mutant channels were expressed in human embryonic kidney tsA-201 cells along with dopamine D2 receptors. Application of quinpirole induced fast (approximately 1 s), pertussis toxin-sensitive inhibition of alpha1A(WT) and alpha1A(R192Q) Ca(2+) currents, consistent with the activation of a membrane-delimited pathway. alpha1A(WT) Ca(2+) currents were inhibited by 62.9 +/- 0.9 % (n = 27), whereas alpha1A(R192Q) Ca(2+) currents were inhibited by only 47.9 +/- 1.8 % (n = 35; P < 0.001). Concentration-response analysis showed that only the extent of inhibition was affected, with no change in agonist potency (EC(50) = 1 nM). Prepulse facilitation, which is a characteristic of voltage-dependent inhibition, was also reduced by the R192Q mutation. However, the kinetics of facilitation and slow activation were not affected, suggesting that G-protein-Ca(2+) channel affinity was unchanged. These results show that the R192Q mutation reduces the G-protein inhibition of P/Q-type Ca(2+) channels, probably by altering mechanisms by which Gbetagamma subunit binding induces a change in channel gating. Altered G-protein modulation and the consequent reduced presynaptic inhibition may contribute to migraine attacks by favouring a persistent state of hyperexcitability.
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