Differential effects of acute hypoxia on the activation of TRPV1 by capsaicin and acidic pH

• Published in: The journal of physiological sciences 2012-03, Vol.62 (2), p.93-103
• Main Authors: Kim, Kyung Soo, Yoo, Hae Young, Park, Kyung Sun, Kim, Jin Kyoung, Zhang, Yin-Hua, Kim, Sung Joon
• Format: Article
• Language: English
• Subjects: 1,2-Dihydroxybenzene-3,5-Disulfonic Acid Disodium Salt - pharmacology; Animals; Antioxidants - pharmacology; Ascorbic Acid - pharmacology; Calcium Signaling - drug effects; Capsaicin; Capsaicin - pharmacology; Cell Hypoxia - physiology; Electrophysiological Phenomena; HEK293 Cells; Humans; Hydrogen Peroxide - pharmacology; Hydrogen-Ion Concentration; Hypoxia; Models, Biological; Original Paper; Patch-Clamp Techniques; Rats; Reactive oxygen species; Reactive Oxygen Species - metabolism; Recombinant Proteins - genetics; Recombinant Proteins - metabolism; Spectrometry, Fluorescence; TRPV Cation Channels - genetics; TRPV Cation Channels - metabolism; TRPV1
• ISSN: 1880-6546; 1880-6562
• DOI: 10.1007/s12576-011-0185-4

Transient receptor potential vanilloid 1 (TRPV1) is a Ca2+-permeable cation channel activated by a variety of physicochemical stimuli. The effect of hypoxia (PO2, 3%) on rat TRPV1 overexpressed in HEK293T has been studied. The basal TRPV1 current (ITRPV1) was partly activated by hypoxia, whereas capsaicin-induced TRPV1 (ITRPV1,Cap) was attenuated. Such changes were also suggested from hypoxia- and capsaicin-induced Ca2+ signals in TRPV1-expressing cells. Regarding plausible changes of reactive oxygen species (ROS) under hypoxia, the effects of antioxidants, vitamin C and tiron, as membrane-impermeable and -permeable, respectively, were tested. Both ITRPV1 and ITRPV1,Cap were increased by vitamin C, while only ITRPV1 was slightly increased by tiron. The hypoxic inhibition of ITRPV1,Cap was still persistent under hypoxia/vitamin C. Interestingly, hypoxia/tiron strongly inhibited both ITRPV1 and ITRPV1,Cap. Also, with vitamin C applied through a pipette solution, hypoxia inhibited ITRPV1 and ITRPV1,Cap. In contrast, hypoxia and hypoxia/tiron had no effect on the ITRPV1 induced by acid (pH 6.2, ITRPV1,Acid). Taken together, hypoxia partly activated TRPV1 while it decreased their sensitivity to capsaicin. Putative changes of ROS under hypoxia might underlie the side-specific effects of ROS on TRPV1: inhibitory at the extracellular and stimulatory at the intracellular side, respectively. The differential effects of hypoxia on ITRPV1,Cap and ITRPV1,Acid suggested that the intracellular ROS increase might attenuate the pharmacological potency of capsaicin.