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TRPC7 is a receptor-operated DAG-activated channel in human keratinocytes.

Abstract : Muscarinic and purinergic receptors expressed in keratinocytes are an important part of a functional system for cell growth. While several aspects of this process are clearly dependent on Ca(2+) homeostasis, less is known about the mechanisms controlling Ca(2+) entry during epidermal receptor stimulation. We used patch-clamp technique to study responses to carbachol (CCh) and adenosine triphosphate (ATP) in HaCaT human keratinocytes. Both agonists induced large currents mediated by cation-selective channels about three times more permeable to Ca(2+) than Na(+), suggesting that they play an important role in receptor-operated Ca(2+) entry. CCh- and ATP-induced currents were inhibited by 1-[6-([(17beta)-3-methoxyestra-1,3,5(10)-trien-17-yl]amino)hexyl]-1H-pyrrole-2,5-dione, a phospholipase C (PLC) blocker. Investigation of the pathways downstream of PLC activation revealed that InsP(3) did not affect the agonist responses. In contrast, 1-oleoyl-2-acetyl-sn-glycerol (OAG), a membrane-permeable analog of 1,2-diacylglycerol (DAG), evoked a similar cation current. This action appears to be direct, since the effects of activators or inhibitors of protein kinase C were comparatively small. Finally, transient receptor potential canonical 7 (TRPC7) specific knockdown by antisense oligonucleotides led to a decrease in ATP- and CCh-induced calcium entry, as well as OAG-evoked current. We concluded that activation of both muscarinic and purinergic receptors via a common DAG-dependent link opens Ca(2+)-permeable TRPC7 channels.
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Contributor : Benjamin Beck Connect in order to contact the contributor
Submitted on : Tuesday, March 13, 2007 - 2:48:29 PM
Last modification on : Thursday, January 20, 2022 - 9:56:02 AM
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Benjamin Beck, Alexander Zholos, Vadym Sydorenko, Morad Roudbaraki, V'Yacheslav Lehen'Kyi, et al.. TRPC7 is a receptor-operated DAG-activated channel in human keratinocytes.. Journal of Investigative Dermatology, Nature Publishing Group, 2006, 126 (9), pp.1982-93. ⟨10.1038/sj.jid.5700352⟩. ⟨inserm-00136352⟩



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