Endogenous TRPV1 stimulation leads to the activation of the inositol phospholipid pathway necessary for sustained Ca2+oscillations.
Sensory neuron subpopulations as well as breast and prostate cancer cells express functional transient receptor potential vanilloid type 1 (TRPV1) ion channels; however little is known how TRPV1 activation leads to biological responses. Agonist-induced activation of TRPV1 resulted in specific spatiotemporal patterns of cytoplasmic Ca2+signals in breast and prostate cancer-derived cells. Capsaicin (CAPS; 50μM) evoked intracellular Ca2+oscillations and/or intercellular Ca2+waves in all cell lines. As evidenced in prostate cancer Du 145 cells, oscillations were largely dependent on the expression of functional TRPV1 channels in the plasma membrane, phospholipase C activation and on the presence of extracellular Ca2+ions. Concomitant oscillations of the mitochondrial matrix Ca2+concentration resulted in mitochondria energization evidenced by increased ATP production. CAPS-induced Ca2+oscillations also occurred in a subset of sensory neurons, yet already at lower CAPS concentrations (1μM). Stimulation of ectopically expressed TRPV1 channels in CAPS-insensitive NIH-3T3 cells didn't provoke CAPS-triggered Ca2+oscillations; rather it resulted in low-magnitude, long-lasting elevations of the cytosolic Ca2+concentration. This indicates that sole TRPV1 activation is not sufficient to generate Ca2+oscillations. Instead the initial TRPV1-mediated signal leads to the activation of the inositol phospholipid pathway. This in turn suffices to generate a biologically relevant frequency-modulated Ca2+signal.
Anatomy, Department of Medicine, University of Fribourg, Route Albert-Gockel 1, Fribourg, CH-1700, Switzerland. Electronic address: laszlo.pecze@unifr.ch.
László
L
Pecze
Anatomy, Department of Medicine, University of Fribourg, Route Albert-Gockel 1, Fribourg, CH-1700, Switzerland.
Walter
W
Blum
Anatomy, Department of Medicine, University of Fribourg, Route Albert-Gockel 1, Fribourg, CH-1700, Switzerland.
Thomas
T
Henzi
Anatomy, Department of Medicine, University of Fribourg, Route Albert-Gockel 1, Fribourg, CH-1700, Switzerland.
Beat
B
Schwaller
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling; D002211:Capsaicin / Q000031:analogs & derivatives / Q000494:pharmacology; D045744:Cell Line, Tumor; D004224:Diterpenes / Q000494:pharmacology; D015870:Gene Expression; D057809:HEK293 Cells; D006801:Humans; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism*; D051379:Mice; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D041681:NIH 3T3 Cells; D061251:Primary Cell Culture; D011984:Sensory Receptor Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D050916:TRPV Cation Channels / Q000235:genetics / Q000378:metabolism*; D012668:Trigeminal Ganglion / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D010738:Type C Phospholipases / Q000235:genetics / Q000378:metabolism*
D004224:Diterpenes; D050916:TRPV Cation Channels; C494482:TRPV1 protein, human; D015544:Inositol 1,4,5-Trisphosphate; D000255:Adenosine Triphosphate; C024353:resiniferatoxin; D010738:Type C Phospholipases; C071423:capsazepine; D002211:Capsaicin; D002118:Calcium
Ca(2+) oscillations; TRPV1; inositol trisphosphate; phospholipase C