Late sodium current blocker GS967 inhibits persistent currents induced by familial hemiplegic migraine type 3 mutations of the SCN1A gene.
FHM3
Migraine treatment
Na+ current inactivation
Persistent current
Voltage gated Na+ channel
Journal
The journal of headache and pain
ISSN: 1129-2377
Titre abrégé: J Headache Pain
Pays: England
ID NLM: 100940562
Informations de publication
Date de publication:
15 Nov 2019
15 Nov 2019
Historique:
received:
25
07
2019
accepted:
29
10
2019
entrez:
16
11
2019
pubmed:
16
11
2019
medline:
26
2
2020
Statut:
epublish
Résumé
Familial hemiplegic migraine (FHM) is a group of genetic migraine, associated with hemiparesis and aura. Three causative different genes have been identified, all of which are involved in membrane ion transport. Among these, SCN1A encodes the voltage-gated Na To obtain a more complete picture, here, we characterized by patch clamp approach the remaining 5 mutations (Q1489H, I1498M, F1499 L, M1500 V, F1661 L) in heterologous expression systems. With the exception of I1498M, all mutants exhibited the same current density as WT and exhibited a shift of the steady state inactivation to more positive voltages, an accelerated recovery from inactivation, and an increase of the persistent current, revealing that most FHM3 mutations induce a gain of function. We also determined the effect of GS967, a late Na In conclusion, late Na
Sections du résumé
BACKGROUND
BACKGROUND
Familial hemiplegic migraine (FHM) is a group of genetic migraine, associated with hemiparesis and aura. Three causative different genes have been identified, all of which are involved in membrane ion transport. Among these, SCN1A encodes the voltage-gated Na
METHODS
METHODS
To obtain a more complete picture, here, we characterized by patch clamp approach the remaining 5 mutations (Q1489H, I1498M, F1499 L, M1500 V, F1661 L) in heterologous expression systems.
RESULTS
RESULTS
With the exception of I1498M, all mutants exhibited the same current density as WT and exhibited a shift of the steady state inactivation to more positive voltages, an accelerated recovery from inactivation, and an increase of the persistent current, revealing that most FHM3 mutations induce a gain of function. We also determined the effect of GS967, a late Na
CONCLUSION
CONCLUSIONS
In conclusion, late Na
Identifiants
pubmed: 31730442
doi: 10.1186/s10194-019-1056-2
pii: 10.1186/s10194-019-1056-2
pmc: PMC6858687
doi:
Substances chimiques
6-(4-(trifluoromethoxy)phenyl)-3-(trifluoromethyl)(1,2,4)triazolo(4,3-a)pyridine
0
NAV1.1 Voltage-Gated Sodium Channel
0
Pyridines
0
SCN1A protein, human
0
Triazoles
0
Sodium
9NEZ333N27
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
107Subventions
Organisme : Fondazione Telethon
ID : GGP17178
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