Biomol Ther  
T-Type Calcium Channels Are Required to Maintain Viability of Neural Progenitor Cells
Ji-Woon Kim1, Hyun Ah Oh1, Sung Hoon Lee2, Ki Chan Kim3, Pyung Hwa Eun1, Mee Jung Ko1, Edson Luck T. Gonzales1, Hana Seung1, Seonmin Kim1, Geon Ho Bahn4 and Chan Young Shin1,3,*
1Department of Pharmacology and Department of Advanced Translational Medicine, School of Medicine, Konkuk University, Seoul 05029, 2College of Pharmacy, Chung-Ang University, Seoul 06974, 3KU Open Innovation Center and IBST, Konkuk University, Seoul 05029, 4Department of Neuropsychiatry, School of Medicine, Kyung Hee University, Seoul 02447, Republic of Korea
E-mail: chanyshin@kku.ac.kr
Tel: +82-2-2030-7834, Fax: +82-2-2030-7899
Received: November 1, 2017; Revised: November 24, 2017; Accepted: November 29, 2017; Published online: February 21, 2018.
© The Korean Society of Applied Pharmacology. All rights reserved.

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.
Keywords: T-type calcium channel, Neural progenitor cells, AKT, GSK3β, Apoptosis, Toxicity


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