T-Type Calcium Channels Are Required to Maintain Viability of Neural Progenitor Cells
Biomolecules & Therapeutics
; : 439-445, 2018.
Artigo
em Inglês
| WPRIM (Pacífico Ocidental)
| ID: wpr-716598
Biblioteca responsável:
WPRO
ABSTRACT
T-type calcium channels are low voltage-activated calcium channels that evoke small and transient calcium currents. Recently, T-type calcium channels have been implicated in neurodevelopmental disorders such as autism spectrum disorder and neural tube defects. However, their function during embryonic development is largely unknown. Here, we investigated the function and expression of T-type calcium channels in embryonic neural progenitor cells (NPCs). First, we compared the expression of T-type calcium channel subtypes (CaV3.1, 3.2, and 3.3) in NPCs and differentiated neural cells (neurons and astrocytes). We detected all subtypes in neurons but not in astrocytes. In NPCs, CaV3.1 was the dominant subtype, whereas CaV3.2 was weakly expressed, and CaV3.3 was not detected. Next, we determined CaV3.1 expression levels in the cortex during early brain development. Expression levels of CaV3.1 in the embryonic period were transiently decreased during the perinatal period and increased at postnatal day 11. We then pharmacologically blocked T-type calcium channels to determine the effects in neuronal cells. The blockade of T-type calcium channels reduced cell viability, and induced apoptotic cell death in NPCs but not in differentiated astrocytes. Furthermore, blocking T-type calcium channels rapidly reduced AKT-phosphorylation (Ser473) and GSK3β-phosphorylation (Ser9). Our results suggest that T-type calcium channels play essential roles in maintaining NPC viability, and T-type calcium channel blockers are toxic to embryonic neural cells, and may potentially be responsible for neurodevelopmental disorders.
Texto completo:
Disponível
Contexto em Saúde:
ODS3 - Meta 3.4 Reduzir as mortes prematuras devido doenças não transmissíveis
Problema de saúde:
Anomalias Congênitas e Cromossômicas
/
Saúde Mental e Transtornos do Comportamento
Base de dados:
WPRIM (Pacífico Ocidental)
Assunto principal:
Células-Tronco
/
Encéfalo
/
Canais de Cálcio
/
Sobrevivência Celular
/
Astrócitos
/
Cálcio
/
Morte Celular
/
Apoptose
/
Canais de Cálcio Tipo T
/
Desenvolvimento Embrionário
Limite:
Gravidez
Idioma:
Inglês
Revista:
Biomolecules & Therapeutics
Ano de publicação:
2018
Tipo de documento:
Artigo