Potentiation of TRPV3 channel function by unsaturated fatty acids.
Transient receptor potential vanilloid (TRPV) channels are polymodal detectors of multiple environmental factors, including temperature, pH, and pressure. Inflammatory mediators enhance TRPV function through multiple signaling pathways. The lipoxygenase and epoxygenase products of arachidonic acid (AA) metabolism have been shown to directly activate TRPV1 and TRPV4, respectively. TRPV3 is a thermosensitive channel with an intermediate temperature threshold of 31-39 degrees C. We have previously shown that TRPV3 is activated by 2-aminoethoxydiphenyl borate (2APB). Here we show that AA and other unsaturated fatty acids directly potentiate 2APB-induced responses of TRPV3 expressed in HEK293 cells, Xenopus oocytes, and mouse keratinocytes. The AA-induced potentiation is observed in intracellular Ca2+ measurement, whole-cell and two-electrode voltage clamp studies, as well as single channel recordings of excised inside-out and outside-out patches. The fatty acid-induced potentiation is not blocked by inhibitors of protein kinase C and thus differs from that induced by the kinase. The potentiation does not require AA metabolism but is rather mimicked by non-metabolizable analogs of AA. These results suggest a novel mechanism regulating the TRPV3 response to inflammation, which differs from TRPV1 and TRPV4, and involves a direct action of free fatty acids on the channel.
Department of Physiology and Cell Biology, The Ohio State University, Columbus, Ohio 43210, USA.
Hong-Zhen
HZ
Hu
Rui
R
Xiao
Chunbo
C
Wang
Na
N
Gao
Craig K
CK
Colton
Jackie D
JD
Wood
Michael X
MX
Zhu
D000818:Animals; D016718:Arachidonic Acid / Q000494:pharmacology; D001896:Boron Compounds / Q000494:pharmacology; D002118:Calcium / Q000032:analysis; D002460:Cell Line; D002478:Cells, Cultured; D004594:Electrophysiology; D004789:Enzyme Activation / Q000502:physiology; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology*; D006801:Humans; D007249:Inflammation / Q000503:physiopathology; D015603:Keratinocytes / Q000737:chemistry / Q000187:drug effects / Q000502:physiology; D007668:Kidney / Q000737:chemistry / Q000187:drug effects / Q000196:embryology / Q000502:physiology; D019787:Linoleic Acid / Q000494:pharmacology; D051379:Mice; D019301:Oleic Acid / Q000494:pharmacology; D009829:Oleic Acids; D009865:Oocytes / Q000737:chemistry / Q000187:drug effects / Q000502:physiology; D018408:Patch-Clamp Techniques; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D050916:TRPV Cation Channels / Q000032:analysis / Q000187:drug effects* / Q000502:physiology*; D029867:Xenopus Proteins / Q000032:analysis / Q000502:physiology
D001896:Boron Compounds; D005231:Fatty Acids, Unsaturated; D009829:Oleic Acids; D050916:TRPV Cation Channels; C459445:TRPV3 protein, human; C486760:Trpv3 protein, mouse; D029867:Xenopus Proteins; D016718:Arachidonic Acid; D019301:Oleic Acid; C011459:elaidic acid; D019787:Linoleic Acid; C109986:2-aminoethoxydiphenyl borate; D011493:Protein Kinase C; D002118:Calcium