Effects of hypotaurine on substantia gelatinosa neurons of the trigeminal subnucleus caudalis in immature mice

Amino Acids. 2016 Dec;48(12):2843-2853. doi: 10.1007/s00726-016-2321-1. Epub 2016 Aug 29.

Abstract

To understand the action and mechanism of hypotaurine, an immediate precursor of taurine, on orofacial nociceptive processing, we examined the direct effects and receptor types involved in hypotaurine-induced responses using the whole-cell patch clamp technique in the substantia gelatinosa (SG) neurons of the trigeminal subnucleus caudalis (Vc) of immature mice. Under the condition of high-chloride pipette solution, hypotaurine elicited inward currents or upward deflections of membrane potential, which increased in a concentration-dependent manner (30-3000 μM) with the EC50 of 663.8 and 337.6 μM, respectively. The responses to 300 µM hypotaurine were reproducible and recovered upon washout. The 300 µM hypotaurine-induced currents were maintained in the presence of TTX, CNQX, and AP5, indicating direct postsynaptic action of hypotaurine on SG neurons. Responses to both low (300 µM) and high (1 or 3 mM) concentrations of hypotaurine were completely and reversibly blocked by the glycine receptor antagonist strychnine (2 µM), but unaffected by the GABAA receptor antagonist gabazine (3 µM) which blocks synaptic GABAA receptors at low concentration. Furthermore, responses to 300 µM hypotaurine and a maximal concentration of glycine (3 mM) were not additive, indicating that hypotaurine and glycine act on the same receptor. Hypotaurine-induced currents were partially antagonized by picrotoxin (50 µM) which blocks homomeric glycine receptors and by bicuculline (10 µM) which is an antagonist of α2 subunit-containing glycine receptors. These results suggest that hypotaurine-induced responses were mediated by glycine receptor activation in the SG neurons and hypotaurine might be used as an effective therapeutics for orofacial pain.

Keywords: Glycine receptor; Orofacial nociception; Postsynaptic; Whole-cell patch clamp.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • GABA-A Receptor Antagonists / administration & dosage
  • Membrane Potentials / drug effects
  • Mice
  • Neurons / drug effects*
  • Neurons / metabolism
  • Patch-Clamp Techniques
  • Pyridazines / administration & dosage
  • Receptors, GABA-A / drug effects
  • Receptors, GABA-A / metabolism
  • Receptors, Glycine / antagonists & inhibitors
  • Receptors, Glycine / genetics
  • Strychnine / administration & dosage
  • Substantia Gelatinosa / drug effects
  • Substantia Gelatinosa / metabolism
  • Substantia Gelatinosa / pathology
  • Synaptic Potentials / drug effects*
  • Synaptic Potentials / genetics
  • Taurine / administration & dosage
  • Taurine / analogs & derivatives*
  • Trigeminal Nuclei / drug effects*
  • Trigeminal Nuclei / metabolism

Substances

  • GABA-A Receptor Antagonists
  • Pyridazines
  • Receptors, GABA-A
  • Receptors, Glycine
  • Taurine
  • hypotaurine
  • gabazine
  • Strychnine