Involvement of voltage-gated K+ and Na+ channels in gastric epithelial cell migration.
Epithelial cell migration plays an important role in gastrointestinal mucosal repair. We previously reported that multiple functional ion channels, including a Ba(2+)-sensitive K(+) inward rectifier K(ir)1.2, 4-aminopyridine (4-AP)-sensitive voltage-gated K(+) channels K(v)1.1, K(v)1.6 and K(v)2.1, and a nifedipine-sensitive, tetrodotoxin (TTX)-insensitive voltage-gated Na(+) channel Na(v)1.5 were expressed in a non-transformed rat gastric epithelial cell line (RGM-1). In the present study, we further investigated whether these ion channels are involved in the modulation of gastric epithelial cell migration. Cell migration was determined by monolayer wound healing assay. Results showed that blockade of K(v) with 4-AP or Na(v)1.5 with nifedipine inhibited RGM-1 cell migration in the absence or presence of epidermal growth factor (EGF), which effectively stimulated RGM-1 cell migration. Moreover, high concentration of TTX mimicked the action of nifedipine, suggesting that the action of nifedipine was mediated through specific blockade of Na(v)1.5. In contrast, inhibition of K(ir)1.2 with Ba(2+), either in basal or EGF-stimulated condition, had no effect on RGM-1 cell migration. In conclusion, the present study demonstrates for the first time that voltage-gated K(+) and Na(+) channels are involved in the modulation of gastric epithelial cell migration.
Wu
William Ka Kei
WK
Department of Pharmacology, Basic Medical Sciences Building, The Chinese University of Hong Kong, Shatin, Hong Kong, China.
Li
Gui Rong
GR
Wong
Tak Ming
TM
Wang
Jian Ying
JY
Yu
Le
L
Cho
Chi Hin
CH
D015761:4-Aminopyridine / Q000494:pharmacology; D000818:Animals; D001464:Barium / Q000494:pharmacology; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects; D004815:Epidermal Growth Factor / Q000494:pharmacology; D004847:Epithelial Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D005753:Gastric Mucosa / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D015640:Ion Channel Gating / Q000187:drug effects; D009543:Nifedipine / Q000494:pharmacology; D026902:Potassium Channel Blockers / Q000494:pharmacology; D024642:Potassium Channels, Voltage-Gated / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D026941:Sodium Channel Blockers / Q000494:pharmacology; D015222:Sodium Channels / Q000235:genetics / Q000378:metabolism*; D013779:Tetrodotoxin / Q000494:pharmacology
D026902:Potassium Channel Blockers; D024642:Potassium Channels, Voltage-Gated; D012333:RNA, Messenger; D026941:Sodium Channel Blockers; D015222:Sodium Channels; D001464:Barium; D013779:Tetrodotoxin; D004815:Epidermal Growth Factor; D015761:4-Aminopyridine; D009543:Nifedipine