Effect of tolbutamide on tetraethylammonium-induced postsynaptic zinc signals at hippocampal mossy fiber-CA3 synapses

Can J Physiol Pharmacol. 2017 Sep;95(9):1058-1063. doi: 10.1139/cjpp-2016-0379. Epub 2017 Jun 27.

Abstract

The application of tetraethylammonium (TEA), a blocker of voltage-dependent potassium channels, can induce long-term potentiation (LTP) in the synaptic systems CA3-CA1 and mossy fiber-CA3 pyramidal cells of the hippocampus. In the mossy fibers, the depolarization evoked by extracellular TEA induces a large amount of glutamate and also of zinc release. It is considered that zinc has a neuromodulatory role at the mossy fiber synapses, which can, at least in part, be due to the activation of presynaptic ATP-dependent potassium (KATP) channels. The aim of this work was to study properties of TEA-induced zinc signals, detected at the mossy fiber region, using the permeant form of the zinc indicator Newport Green. The application of TEA caused a depression of those signals that was partially blocked by the KATP channel inhibitor tolbutamide. After the removal of TEA, the signals usually increased to a level above baseline. These results are in agreement with the idea that intense zinc release during strong synaptic events triggers a negative feedback action. The zinc depression, caused by the LTP-evoking chemical stimulation, turns into potentiation after TEA washout, suggesting the existence of a correspondence between the observed zinc potentiation and TEA-evoked mossy fiber LTP.

Keywords: CA3; canaux calciques dépendants du voltage; fibre moussue; hippocampe; hippocampus; long-term potentiation; mossy fiber; potentialisation à long terme; tetraethylammonium; tétraéthylammonium; voltage-dependent calcium channel.

MeSH terms

  • Animals
  • CA3 Region, Hippocampal / cytology*
  • CA3 Region, Hippocampal / drug effects
  • Female
  • KATP Channels / metabolism
  • Long-Term Potentiation / drug effects
  • Mossy Fibers, Hippocampal / drug effects*
  • Potassium Channel Blockers / pharmacology
  • Pregnancy
  • Rats
  • Rats, Wistar
  • Signal Transduction / drug effects*
  • Synapses / drug effects*
  • Synapses / metabolism
  • Tetraethylammonium / pharmacology*
  • Tolbutamide / pharmacology*
  • Zinc / metabolism*

Substances

  • KATP Channels
  • Potassium Channel Blockers
  • Tetraethylammonium
  • Tolbutamide
  • Zinc