title: Involvement of Kv1.1 and Nav1.5 in proliferation of gastric epithelial cells.
abstract: 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.
authors.affiliation: Department of Pharmacology, Faculty of Medicine, The University of Hong Kong, Hong Kong, China.
authors.forename: William Ka Kei
authors.initials: WK
authors.lastname: Wu
authors.forename: Gui Rong
authors.initials: GR
authors.lastname: Li
authors.forename: Helen Pui Shan
authors.initials: HP
authors.lastname: Wong
authors.forename: Marco King Cheung
authors.initials: MK
authors.lastname: Hui
authors.forename: Emily Kin Ki
authors.initials: EK
authors.lastname: Tai
authors.forename: Emily Kai Yee
authors.initials: EK
authors.lastname: Lam
authors.forename: Vivian Yvonne
authors.initials: VY
authors.lastname: Shin
authors.forename: Yi Ni
authors.initials: YN
authors.lastname: Ye
authors.forename: Peng
authors.initials: P
authors.lastname: Li
authors.forename: Ying Hua
authors.initials: YH
authors.lastname: Yang
authors.forename: Jiing Chyuan
authors.initials: JC
authors.lastname: Luo
authors.forename: Chi Hin
authors.initials: CH
authors.lastname: Cho
mesh_terms: 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*
chemical_list: 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