Academic Journal
Familial hemiplegic migraine type 1 mutations W1684R and V1696I alter G protein-mediated regulation of Ca(V)2.1 voltage-gated calcium channels.
| العنوان: | Familial hemiplegic migraine type 1 mutations W1684R and V1696I alter G protein-mediated regulation of Ca(V)2.1 voltage-gated calcium channels. |
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| المؤلفون: | Garza-López, Edgar, Sandoval, Alejandro, González-Ramírez, Ricardo, Gandini, María, A., van den Maagdenberg, Arn, de Waard, Michel, Felix, Ricardo |
| المساهمون: | Department of Cell Biology, Center for Research and Advanced Studies of the National Polytechnic Institute (CINVESTAV-IPN), School of Medicine FES Istacala, Universidad Nacional Autónoma de México = National Autonomous University of Mexico (UNAM), Department of Molecular Biology and Histocompatibility, Dr. Manuel Gea González General Hospital, Departments of Human Genetics & Neurology, Leiden University Medical Center (LUMC), Universiteit Leiden = Leiden University-Universiteit Leiden = Leiden University, INSERM U836, équipe 3, Canaux calciques, fonctions et pathologies, Grenoble Institut des Neurosciences (GIN), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), Conacyt (128707), PAPIIT (IN221011) |
| المصدر: | ISSN: 0006-3002 ; BBA - Biochimica et Biophysica Acta ; https://inserm.hal.science/inserm-00757116 ; BBA - Biochimica et Biophysica Acta, 2012, 1822 (8), pp.1238-46. ⟨10.1016/j.bbadis.2012.04.008⟩. |
| بيانات النشر: | CCSD Elsevier |
| سنة النشر: | 2012 |
| المجموعة: | Université Grenoble Alpes: HAL |
| مصطلحات موضوعية: | [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology |
| الوصف: | International audience ; Familial hemiplegic migraine type 1 (FHM-1) is a monogenic form of migraine with aura that is characterized by recurrent attacks of a typical migraine headache with transient hemiparesis during the aura phase. In a subset of patients, additional symptoms such as epilepsy and cerebellar ataxia are part of the clinical phenotype. FHM-1 is caused by missense mutations in the CACNA1A gene that encodes the pore-forming subunit of Ca(V)2.1 voltage-gated Ca(2+) channels. Although the functional effects of an increasing number of FHM-1 mutations have been characterized, knowledge on the influence of most of these mutations on G protein regulation of channel function is lacking. Here, we explored the effects of G protein-dependent modulation on mutations W1684R and V1696I which cause FHM-1 with and without cerebellar ataxia, respectively. Both mutations were introduced into the human Ca(V)2.1α(1) subunit and their functional consequences investigated after heterologous expression in human embryonic kidney 293 (HEK-293) cells using patch-clamp recordings. When co-expressed along with the human μ-opioid receptor, application of the agonist [d-Ala2, N-MePhe4, Gly-ol]-enkephalin (DAMGO) inhibited currents through both wild-type (WT) and mutant Ca(V)2.1 channels, which is consistent with the known modulation of these channels by G protein-coupled receptors. Prepulse facilitation, which is a way to characterize the relief of direct voltage-dependent G protein regulation, was reduced by both FHM-1 mutations. Moreover, the kinetic analysis of the onset and decay of facilitation showed that the W1684R and V1696I mutations affect the apparent dissociation and reassociation rates of the Gβγ dimer from the channel complex, suggesting that the G protein-Ca(2+) channel affinity may be altered by the mutations. These biophysical studies may shed new light on the pathophysiology underlying FHM-1. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| Relation: | info:eu-repo/semantics/altIdentifier/pmid/22549042; PUBMED: 22549042 |
| DOI: | 10.1016/j.bbadis.2012.04.008 |
| الاتاحة: | https://inserm.hal.science/inserm-00757116 https://inserm.hal.science/inserm-00757116v1/document https://inserm.hal.science/inserm-00757116v1/file/Garza-Lopez_2012_Familial_MA.pdf https://doi.org/10.1016/j.bbadis.2012.04.008 |
| Rights: | info:eu-repo/semantics/OpenAccess |
| رقم الانضمام: | edsbas.DD5322F7 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1016/j.bbadis.2012.04.008 |
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