Int J Oral Biol.  2017 Jun;42(2):55-61. 10.11620/IJOB.2017.42.2.055.

Action of Mitochondrial Substrates on Neuronal Excitability in Rat Substantia Gelatinosa Neurons

• Lee HI
• Chun SW

• KMID: 2385806
• DOI: http://doi.org/10.11620/IJOB.2017.42.2.055

Abstract

Recent studies indicate that mitochondria are an important source of reactive oxygen species (ROS) in the spinal dorsal horn. In our previous study, application of malate, a mitochondrial electron transport complex I substrate, induced a membrane depolarization, which was inhibited by pretreatment with ROS scavengers. In the present study, we used patch clamp recording in the substantia geletinosa (SG) neurons of spinal slices, to investigate the cellular mechanism of mitochondrial ROS on neuronal excitability. DNQX (an AMPA receptor antagonist) and AP5 (an NMDA receptor antagonist) decreased the malate-induced depolarization. In an external calcium free solution and addition of tetrodotoxin (TTX) for blockade of synaptic transmission, the malateinduced depolarization remained unchanged. In the presence of DNQX, AP5 and AP3 (a group I metabotropic glutamate receptor (mGluR) antagonist), glutamate depolarized the membrane potential, which was suppressed by PBN. However, oligomycin (a mitochondrial ATP synthase inhibitor) or PPADS (a P2 receptor inhibitor) did not affect the substrates-induced depolarization. These results suggest that mitochondrial substrate-induced ROS in SG neuron directly acts on the postsynaptic neuron, therefore increasing the ion influx via glutamate receptors.

Keyword

Malate; Membrane excitability; Reactive oxygen species; SG neurons

MeSH Terms

Animals
Calcium
Electron Transport Complex I
Glutamic Acid
Membrane Potentials
Membranes
Mitochondria
Mitochondrial Proton-Translocating ATPases
N-Methylaspartate
Neurons*
Oligomycins
Rats*
Reactive Oxygen Species
Receptors, AMPA
Receptors, Glutamate
Receptors, Metabotropic Glutamate
Spinal Cord Dorsal Horn
Substantia Gelatinosa*
Synaptic Transmission
Tetrodotoxin
Calcium
Electron Transport Complex I
Glutamic Acid
Mitochondrial Proton-Translocating ATPases
N-Methylaspartate
Oligomycins
Reactive Oxygen Species
Receptors, AMPA
Receptors, Glutamate
Receptors, Metabotropic Glutamate
Tetrodotoxin