title: Expression-dependent pharmacology of transient receptor potential vanilloid subtype 1 channels in Xenopus laevis oocytes.
abstract: Transient receptor potential vanilloid subfamily member 1 channels are polymodal sensors of noxious stimuli and integral players in thermosensation, inflammation and pain signaling. It has been shown previously that under prolonged stimulation, these channels show dynamic pore dilation, providing a pathway for large and otherwise relatively impermeant molecules. Further, we have shown recently that these nonselective cation channels, when activated by capsaicin, are potently and reversibly blocked by external application of quaternary ammonium compounds and local anesthetics. Here we describe a novel phenomenon in transient receptor potential channel pharmacology whereby their expression levels in Xenopus laevis oocytes, as assessed by the magnitude of macroscopic currents, are negatively correlated with extracellular blocker affinity: small current densities give rise to nanomolar blockade by quaternary ammoniums and this affinity decreases linearly as current density increases. Possible mechanisms to explain these data are discussed in light of similar observations in other channels and receptors.
authors: Department of Anesthesiology, Pharmacology & Therapeutics, The University of British Columbia, Vancouver, BC, Canada.
authors: Ricardo E
authors: RE
authors: Rivera-Acevedo
authors: Stephan A
authors: SA
authors: Pless
authors: Stephan K W
authors: SK
authors: Schwarz
authors: Christopher A
authors: CA
authors: Ahern
mesh_terms: D000818:Animals; D015870:Gene Expression / Q000187:drug effects; D007700:Kinetics; D008012:Lidocaine / Q000031:analogs & derivatives* / Q000494:pharmacology; D009865:Oocytes / Q000187:drug effects / Q000378:metabolism*; D000644:Quaternary Ammonium Compounds / Q000494:pharmacology; D050916:TRPV Cation Channels / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D029867:Xenopus Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D014982:Xenopus laevis / Q000235:genetics* / Q000378:metabolism
chemical_list: D000644:Quaternary Ammonium Compounds; D050916:TRPV Cation Channels; C550099:TRPV1 protein, Xenopus; D029867:Xenopus Proteins; C012647:QX-314; D008012:Lidocaine
keywords: TRP channels; expression-dependent phenomena; pharmacology