Involvement of Kv1.1 and Nav1.5 in proliferation of gastric epithelial cells.
In the present study, patch clamp experiments demonstrated the expression of multiple ionic currents, including a Ba2+-sensitive inward rectifier K+ current (IKir), a 4-aminopyridine- (4-AP) sensitive delayed rectifier K+ current (IKDR), and a nifedipine-sensitive, tetrodotoxin-resistant inward Na+ current (INa.TTXR) in the non-transformed rat gastric epithelial cell line RGM-1. RT-PCR revealed molecular identities of mRNAs for the functional ionic currents, including Kir1.2 for IKir, Kv1.1, Kv1.6, and Kv2.1 for IKDR, and Nav1.5 for INa.TTXR. Pharmacologic blockade of Kv and Nav, but not Kir, suppressed RGM-1 cell proliferation. To further elucidate which subtypes of the ion channels were involved in cell proliferation, RNA interference was employed to knockdown specific gene expression. Downregulation of Kv1.1 or Nav1.5 by RNA interference suppressed RGM-1 cell proliferation. To conclude, our study is the first to delineate the expression of ion channels and their functions as growth modulators in gastric epithelial cells.
Wu
William Ka Kei
WK
Department of Pharmacology, Faculty of Medicine, The University of Hong Kong, Hong Kong, China.
Li
Gui Rong
GR
Wong
Helen Pui Shan
HP
Hui
Marco King Cheung
MK
Tai
Emily Kin Ki
EK
Lam
Emily Kai Yee
EK
Shin
Vivian Yvonne
VY
Ye
Yi Ni
YN
Li
Peng
P
Yang
Ying Hua
YH
Luo
Jiing Chyuan
JC
Cho
Chi Hin
CH
D015761:4-Aminopyridine / Q000494:pharmacology; D000818:Animals; D001464:Barium / Q000494:pharmacology; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects*; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D005753:Gastric Mucosa / Q000166:cytology; D015870:Gene Expression / Q000235:genetics; D051662:Kv1.1 Potassium Channel / Q000235:genetics / Q000502:physiology*; D062554:NAV1.5 Voltage-Gated Sodium Channel; D009543:Nifedipine / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D011188:Potassium / Q000378:metabolism; D015221:Potassium Channels / Q000235:genetics / Q000502:physiology; D034741:RNA, Small Interfering / Q000235:genetics; D051381:Rats; D012964:Sodium / Q000378:metabolism; D015222:Sodium Channels / Q000235:genetics / Q000502:physiology*
D062554:NAV1.5 Voltage-Gated Sodium Channel; D015221:Potassium Channels; D034741:RNA, Small Interfering; C568322:Scn5a protein, rat; D015222:Sodium Channels; D051662:Kv1.1 Potassium Channel; D001464:Barium; D012964:Sodium; D015761:4-Aminopyridine; D009543:Nifedipine; D011188:Potassium