Hyposmotic stimulation-induced nitric oxide production in outer hair cells of the guinea pig cochlea

Hear Res. 2007 Aug;230(1-2):93-104. doi: 10.1016/j.heares.2007.05.010.

Abstract

Nitric oxide (NO) production during hyposmotic stimulation in outer hair cells (OHCs) of the guinea pig cochlea was investigated using the NO sensitive dye DAF-2. Simultaneous measurement of the cell length and NO production showed rapid hyposmotic-induced cell swelling to precede NO production in OHCs. Hyposmotic stimulation failed to induce NO production in the Ca2+-free solution. L-NG-nitroarginine methyl ester (L-NAME), a non-specific NO synthase inhibitor and gadolinium, a stretch-activated channel blocker inhibited the hyposmotic stimulation-induced NO production whereas suramin, a P2 receptor antagonist did not. S-nitroso-N-acetylpenicillamine (SNAP), a NO donor inhibited the hyposmotic stimulation-induced increase in the intracellular Ca2+ concentrations ([Ca2+]i) while L-NAME enhanced it. 1H-[1,2,4]oxadiazole[4,3a]quinoxalin-1-one, an inhibitor of guanylate cyclase and KT5823, an inhibitor of cGMP-dependent protein kinase (PKG) mimicked effects of L-NAME on the Ca2+ response. Transient receptor potential vanilloid 4 (TRPV4), an osmo- and mechanosensitive channel was expressed in the OHCs by means of immunohistochemistry. 4alpha-phorbol 12,13-didecanoate, a TRPV4 synthetic activator, induced NO production in OHCs. These results suggest that hyposmotic stimulation can induce NO production by the [Ca2+]i increase, which is presumably mediated by the activation of TRPV4 in OHCs. NO conversely inhibits the Ca2+ response via the NO-cGMP-PKG pathway by a feedback mechanism.

Publication types

  • Corrected and Republished Article

MeSH terms

  • 8-Bromo Cyclic Adenosine Monophosphate / pharmacology
  • Animals
  • Calcium / metabolism
  • Carbazoles / pharmacology
  • Cell Size* / drug effects
  • Cells, Cultured
  • Cyclic GMP / metabolism
  • Cyclic GMP-Dependent Protein Kinases / antagonists & inhibitors
  • Cyclic GMP-Dependent Protein Kinases / metabolism
  • Enzyme Inhibitors / pharmacology
  • Gadolinium / pharmacology
  • Guanylate Cyclase / antagonists & inhibitors
  • Guanylate Cyclase / metabolism
  • Guinea Pigs
  • Hair Cells, Auditory, Outer / drug effects
  • Hair Cells, Auditory, Outer / metabolism*
  • Hypotonic Solutions
  • Indoles / pharmacology
  • Kinetics
  • Membrane Potentials
  • NG-Nitroarginine Methyl Ester / pharmacology
  • Nitric Oxide / metabolism*
  • Nitric Oxide Donors / pharmacology
  • Nitric Oxide Synthase / antagonists & inhibitors
  • Nitric Oxide Synthase / metabolism
  • Organ of Corti / cytology
  • Organ of Corti / drug effects
  • Organ of Corti / metabolism*
  • Osmotic Pressure
  • Phorbol Esters / pharmacology
  • Potassium / metabolism
  • Purinergic P2 Receptor Antagonists
  • Receptors, Purinergic P2 / metabolism
  • S-Nitroso-N-Acetylpenicillamine / pharmacology
  • Signal Transduction* / drug effects
  • Sodium Chloride / metabolism
  • Suramin / pharmacology
  • TRPV Cation Channels / agonists
  • TRPV Cation Channels / metabolism

Substances

  • Carbazoles
  • Enzyme Inhibitors
  • Hypotonic Solutions
  • Indoles
  • Nitric Oxide Donors
  • Phorbol Esters
  • Purinergic P2 Receptor Antagonists
  • Receptors, Purinergic P2
  • TRPV Cation Channels
  • KT 5823
  • 8-Bromo Cyclic Adenosine Monophosphate
  • Nitric Oxide
  • Sodium Chloride
  • Suramin
  • S-Nitroso-N-Acetylpenicillamine
  • Gadolinium
  • Nitric Oxide Synthase
  • Cyclic GMP-Dependent Protein Kinases
  • Guanylate Cyclase
  • Cyclic GMP
  • gadolinium chloride
  • Potassium
  • Calcium
  • NG-Nitroarginine Methyl Ester