PMID- 15126053 OWN - NLM STAT- MEDLINE DCOM- 20041207 LR - 20131121 IS - 0143-4160 (Print) IS - 0143-4160 (Linking) VI - 36 IP - 1 DP - 2004 Jul TI - TRPV channels and modulation by hepatocyte growth factor/scatter factor in human hepatoblastoma (HepG2) cells. PG - 19-28 AB - Using patch clamp and Ca(2+) imaging techniques, we have studied Ca(2+) entry pathways in human hepatoblastoma (HepG2) cells. These cells express the mRNA of TRPV1, TRPV2, TRPV3 and TRPV4 channels, but not those of TRPV5 and TRPV6. Functional assessment showed that capsaicin (10 microM), 4alpha-phorbol-12,13-didecanoate (4alphaPDD, 1 microM), arachidonic acid (10 microM), hypotonic stress, and heat all stimulated increases in [Ca(2+)](i) within minutes. The increase in [Ca(2+)](i) depended on extracellular Ca(2+) and on the transmembrane potential, which indicated that both driving forces affected Ca(2+) entry. Capsaicin also stimulated an increase in [Ca(2+)](i) in nominally Ca(2+)-free solutions, which was compatible with the receptor functioning as a Ca(2+) release channel. Hepatocyte growth factor/scatter factor (HGF/SF) modulated Ca(2+) entry. Ca(2+) influx was greater in HepG2 cells incubated with HGF/SF (20 ng/ml for 20 h) compared with non-stimulated cells, but this occurred only in those cells with a migrating phenotype as determined by presence of a lamellipodium and trailing footplate. The effect of capsaicin on [Ca(2+)](i) was greater in migrating HGF/SF-treated cells, and this was inhibited by capsazepine. The difference between control and HGF/SF-treated cells was not found in Ca(2+)-free solutions. 4alphaPDD also had no greater effect on HGF/SF-treated cells. We conclude that TRPV1 and TRPV4 channels provide Ca(2+) entry pathways in HepG2 cells. HGF/SF increases Ca(2+) entry via TRPV1, but not via TRPV4. This rise in [Ca(2+)](i) may constitute an early response of a signalling cascade that gives rise to cell locomotion and the migratory phenotype. FAU - Vriens, Joris AU - Vriens J AD - Department of Physiology, Campus Gasthuisberg, Katholieke Universiteit, B-3000 Leuven, Belgium. FAU - Janssens, Annelies AU - Janssens A FAU - Prenen, Jean AU - Prenen J FAU - Nilius, Bernd AU - Nilius B FAU - Wondergem, Robert AU - Wondergem R LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - Netherlands TA - Cell Calcium JT - Cell calcium JID - 8006226 RN - 0 (Cation Transport Proteins) RN - 0 (Hypotonic Solutions) RN - 0 (Ion Channels) RN - 0 (Phorbol Esters) RN - 0 (RNA, Messenger) RN - 27YG812J1I (Arachidonic Acid) RN - 54870-24-5 (4-O-methyl-phorbol-12,13-didecanoate) RN - 67256-21-7 (Hepatocyte Growth Factor) RN - S07O44R1ZM (Capsaicin) RN - SY7Q814VUP (Calcium) SB - IM MH - Arachidonic Acid/pharmacology MH - Calcium/metabolism/physiology MH - Capsaicin/pharmacology MH - Cation Transport Proteins/genetics/*physiology MH - Cell Line, Tumor MH - Cell Movement/*drug effects/physiology MH - Gene Expression MH - Hepatoblastoma MH - Hepatocyte Growth Factor/*pharmacology MH - Hepatocytes/drug effects/*metabolism MH - Hot Temperature MH - Humans MH - Hypotonic Solutions/pharmacology MH - Ion Channels/*classification/drug effects/*physiology MH - Models, Biological MH - Patch-Clamp Techniques MH - Phorbol Esters/pharmacology MH - RNA, Messenger/metabolism MH - Time Factors EDAT- 2004/05/06 05:00 MHDA- 2004/12/16 09:00 CRDT- 2004/05/06 05:00 PHST- 2003/09/24 00:00 [received] PHST- 2003/11/18 00:00 [revised] PHST- 2003/11/19 00:00 [accepted] PHST- 2004/05/06 05:00 [pubmed] PHST- 2004/12/16 09:00 [medline] PHST- 2004/05/06 05:00 [entrez] AID - S0143416003002471 [pii] AID - 10.1016/j.ceca.2003.11.006 [doi] PST - ppublish SO - Cell Calcium. 2004 Jul;36(1):19-28. doi: 10.1016/j.ceca.2003.11.006.