BIOLOGICAL ANTIARRHYTHMICS-SODIUM CHANNEL INTERACTING PROTEINS.
Trans Am Clin Climatol Assoc
; 133: 136-148, 2023.
Article
en En
| MEDLINE
| ID: mdl-37701589
ABSTRACT
Voltage gated Na channels (NaV) are essential for excitation of tissues. Mutations in NaVs cause a spectrum of human disease from autism and epilepsy to cardiac arrhythmias to skeletal myotonias. The carboxyl termini (CT) of NaV channels are hotspots for disease-causing mutations and are richly invested with protein interaction sites. We have focused on the regulation of NaV by two proteins that bind in this region calmodulin (CaM) and non-secreted fibroblast growth factors (iFGF or FHF). CaM regulates NaV gating, mediating Ca2+-dependent inactivation (CDI) in a channel isoform-specific manner, while Ca2+-free CaM (apo-CaM) binding broadly regulates NaV opening and suppresses the arrhythmogenic late Na current (INa-L). FHFs inhibit CDI, in NaV isoforms that exhibit this property, and potently suppress INa-L, the latter requiring the amino terminus of the FHF. A peptide comprised of the first 39 amino acids of FHF1A is sufficient to inhibit INa-L, constituting a credible specific antiarrhythmic.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Canales de Sodio
/
Factores de Crecimiento de Fibroblastos
Límite:
Humans
Idioma:
En
Revista:
Trans Am Clin Climatol Assoc
Año:
2023
Tipo del documento:
Article