T-Type Calcium Channels Are Required to Maintain Viability of Neural Progenitor Cells.
10.4062/biomolther.2017.223
- Author:
Ji Woon KIM
1
;
Hyun Ah OH
;
Sung Hoon LEE
;
Ki Chan KIM
;
Pyung Hwa EUN
;
Mee Jung KO
;
Edson Luck T GONZALES
;
Hana SEUNG
;
Seonmin KIM
;
Geon Ho BAHN
;
Chan Young SHIN
Author Information
1. Department of Pharmacology and Department of Advanced Translational Medicine, School of Medicine, Konkuk University, Seoul 05029, Republic of Korea. chanyshin@kku.ac.kr
- Publication Type:Original Article
- Keywords:
T-type calcium channel;
Neural progenitor cells;
AKT;
GSK3β;
Apoptosis;
Toxicity
- MeSH:
Apoptosis;
Astrocytes;
Autism Spectrum Disorder;
Brain;
Calcium;
Calcium Channels;
Calcium Channels, T-Type*;
Cell Death;
Cell Survival;
Embryonic Development;
Female;
Neural Tube Defects;
Neurodevelopmental Disorders;
Neurons;
Pregnancy;
Stem Cells*
- From:Biomolecules & Therapeutics
2018;26(5):439-445
- CountryRepublic of Korea
- Language:English
-
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.
