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.