Inhibitory synaptic transmission is impaired at higher extracellular Ca2+ concentrations in Scn1a+/- mouse model of Dravet syndrome.
Sci Rep
; 11(1): 10634, 2021 05 20.
Article
en En
| MEDLINE
| ID: mdl-34017040
ABSTRACT
Dravet syndrome (DS) is an intractable form of childhood epilepsy that occurs in infancy. More than 80% of all patients have a heterozygous abnormality in the SCN1A gene, which encodes a subunit of Na+ channels in the brain. However, the detailed pathogenesis of DS remains unclear. This study investigated the synaptic pathogenesis of this disease in terms of excitatory/inhibitory balance using a mouse model of DS. We show that excitatory postsynaptic currents were similar between Scn1a knock-in neurons (Scn1a+/- neurons) and wild-type neurons, but inhibitory postsynaptic currents were significantly lower in Scn1a+/- neurons. Moreover, both the vesicular release probability and the number of inhibitory synapses were significantly lower in Scn1a+/- neurons compared with wild-type neurons. There was no proportional increase in inhibitory postsynaptic current amplitude in response to increased extracellular Ca2+ concentrations. Our study revealed that the number of inhibitory synapses is significantly reduced in Scn1a+/- neurons, while the sensitivity of inhibitory synapses to extracellular Ca2+ concentrations is markedly increased. These data suggest that Ca2+ tethering in inhibitory nerve terminals may be disturbed following the synaptic burst, likely leading to epileptic symptoms.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Calcio
/
Epilepsias Mioclónicas
/
Transmisión Sináptica
/
Espacio Extracelular
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Canal de Sodio Activado por Voltaje NAV1.1
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Inhibición Neural
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Sci Rep
Año:
2021
Tipo del documento:
Article
País de afiliación:
Japón