title: TRP channels are involved in mediating hypercapnic Ca2+ responses in rat glia-rich medullary cultures independent of extracellular pH.
abstract: The medulla contains central chemosensitive cells important for the maintenance of blood gas and pH homeostasis. To identify the intrinsic chemosensitive cells, we measured responses of intracellular Ca(2+) ([Ca(2+)](i)) and H(+) ([H(+)](i)), and membrane potential of rat primary-cultured medullary cells to 6-s exposure to acidosis. The cells showed transient [Ca(2+)](i) increases to extracellular pH 6.8, which was inhibited by the specific ASIC1a blocker (psalmotoxin-1), but did not respond to pH 7.1 in the HEPES-buffered solution. Isocapnic acidosis induced no changes in [Ca(2+)](i), whereas hypercapnic acidosis induced a remarkable Ca(2+) response and an increase in membrane potential in the HCO(3)(-)-buffered solution (pH 7.1). In glia-rich cultures, intracellular acidification preceded the hypercapnic acidosis-induced Ca(2+) response, and acetazolamide, a carbonic anhydrase inhibitor suppressed these responses. Transient receptor potential (TRP) channel broad-spectrum blockers Ni(2+) and ruthenium red, and a TRPV1- and TRPM8-specific blocker N-(4-tertiarybutylphenyl)-4-(3-chloropyridin-2-yl)-tetrahydropyrazine-1(2H)-carbox-amide attenuated the hypercapnic acidosis-induced Ca(2+) response. Subpopulations of cells that exhibited the hypercapnic acidosis-induced Ca(2+) response also responded to the application of capsaicin (TRPV1 agonist) and menthol (TRPM8 agonist). These results suggest that the TRP channel family partially mediates the fast hypercapnic acidosis-induced Ca(2+) response via changes in [H(+)](i) and is a candidate of central chemosensing proteins.
authors: Department of Physiology, Hyogo College of Medicine, Mukogawa-cho, Nishinomiya, Japan.
authors: Yutaka
authors: Y
authors: Hirata
authors: Yoshitaka
authors: Y
authors: Oku
mesh_terms: D000138:Acidosis / Q000378:metabolism / Q000473:pathology; D000818:Animals; D020013:Calcium Signaling / Q000502:physiology*; D002478:Cells, Cultured; D018920:Coculture Techniques; D000242:Cyclic AMP / Q000096:biosynthesis; D006152:Cyclic GMP / Q000096:biosynthesis; D045604:Extracellular Fluid / Q000378:metabolism; D005110:Extracellular Space / Q000378:metabolism / Q000502:physiology*; D006863:Hydrogen-Ion Concentration; D006935:Hypercapnia / Q000378:metabolism* / Q000473:pathology*; D042541:Intracellular Space / Q000378:metabolism / Q000502:physiology; D008526:Medulla Oblongata / Q000196:embryology / Q000378:metabolism / Q000473:pathology; D009457:Neuroglia / Q000378:metabolism* / Q000473:pathology / Q000502:physiology; D009474:Neurons / Q000378:metabolism / Q000473:pathology / Q000502:physiology; D018408:Patch-Clamp Techniques; D051381:Rats; D017208:Rats, Wistar; D050051:Transient Receptor Potential Channels / Q000502:physiology*; D015854:Up-Regulation / Q000502:physiology
chemical_list: D050051:Transient Receptor Potential Channels; D000242:Cyclic AMP; D006152:Cyclic GMP