Ca(2+) signaling evoked by activation of Na(+) channels and Na(+)/Ca(2+) exchangers is required for GABA-induced NG2 cell migration.
NG2 cells originate from various brain regions and migrate to their destinations during early development. These cells express voltage-gated Na(+) channels but fail to produce typical action potentials. The physiological role of Na(+) channels in these cells is unclear. We found that GABA induces membrane depolarization and Ca(2+) elevation in NG2 cells, a process requiring activation of GABA(A) receptors, Na(+) channels, and Na(+)/Ca(2+) exchangers (NCXs), but not Ca(2+) channels. We have identified a persistent Na(+) current in these cells that may underlie the GABA-induced pathway of prolonged Na(+) elevation, which in turn triggers Ca(2+) influx via NCXs. This unique Ca(2+) signaling pathway is further shown to be involved in the migration of NG2 cells. Thus, GABAergic signaling mediated by sequential activation of GABA(A) receptors, noninactivating Na(+) channels, and NCXs may play an important role in the development and function of NG2 glial cells in the brain.
Tong
Xiao-ping
XP
Institute of Neuroscience and State Key Laboratory of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
Li
Xiang-yao
XY
Zhou
Bing
B
Shen
Wanhua
W
Zhang
Zhi-jun
ZJ
Xu
Tian-le
TL
Duan
Shumin
S
D000818:Animals; D020013:Calcium Signaling / Q000187:drug effects*; D002465:Cell Movement / Q000187:drug effects*; D002478:Cells, Cultured; D015536:Down-Regulation / Q000187:drug effects; D006096:Gramicidin / Q000494:pharmacology; D006624:Hippocampus / Q000166:cytology; D015640:Ion Channel Gating / Q000187:drug effects*; D008564:Membrane Potentials / Q000187:drug effects; D034741:RNA, Small Interfering / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000378:metabolism; D012964:Sodium / Q000378:metabolism; D015222:Sodium Channels / Q000378:metabolism*; D019831:Sodium-Calcium Exchanger / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology*
D034741:RNA, Small Interfering; D011963:Receptors, GABA-A; D015222:Sodium Channels; D019831:Sodium-Calcium Exchanger; D006096:Gramicidin; D005680:gamma-Aminobutyric Acid; D012964:Sodium