Biomolecules & Therapeutics

The Korean Society of Applied Pharmacology (한국응용약물학회)
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T-Type Calcium Channels Are Required to Maintain Viability of Neural Progenitor Cells

  • Kim, Ji-Woon (Department of Pharmacology and Department of Advanced Translational Medicine, School of Medicine, Konkuk University) ;
  • Oh, Hyun Ah (Department of Pharmacology and Department of Advanced Translational Medicine, School of Medicine, Konkuk University) ;
  • Lee, Sung Hoon (College of Pharmacy, Chung-Ang University) ;
  • Kim, Ki Chan (KU Open Innovation Center and IBST, Konkuk University) ;
  • Eun, Pyung Hwa (Department of Pharmacology and Department of Advanced Translational Medicine, School of Medicine, Konkuk University) ;
  • Ko, Mee Jung (Department of Pharmacology and Department of Advanced Translational Medicine, School of Medicine, Konkuk University) ;
  • Gonzales, Edson Luck T. (Department of Pharmacology and Department of Advanced Translational Medicine, School of Medicine, Konkuk University) ;
  • Seung, Hana (Department of Pharmacology and Department of Advanced Translational Medicine, School of Medicine, Konkuk University) ;
  • Kim, Seonmin (Department of Pharmacology and Department of Advanced Translational Medicine, School of Medicine, Konkuk University) ;
  • Bahn, Geon Ho (Department of Neuropsychiatry, School of Medicine, Kyung Hee University) ;
  • Shin, Chan Young (Department of Pharmacology and Department of Advanced Translational Medicine, School of Medicine, Konkuk University)
  • Received : 2017.11.01
  • Accepted : 2017.11.29
  • Published : 2018.09.01
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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 $GSK3{\beta}$-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

References

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