Korean J Physiol Pharmacol.  2015 Mar;19(2):177-181. 10.4196/kjpp.2015.19.2.177.

Low Non-NMDA Receptor Current Density as Possible Protection Mechanism from Neurotoxicity of Circulating Glutamate on Subfornical Organ Neurons in Rats

• Chong W
• Kim SN
• Han SK
• Lee SY
• Ryu PD

• KMID: 2285570
• DOI: http://doi.org/10.4196/kjpp.2015.19.2.177

Abstract

The subfornical organ (SFO) is one of circumventricular organs characterized by the lack of a normal blood brain barrier. The SFO neurons are exposed to circulating glutamate (60~100 microM), which may cause excitotoxicity in the central nervous system. However, it remains unclear how SFO neurons are protected from excitotoxicity caused by circulating glutamate. In this study, we compared the glutamate-induced whole cell currents in SFO neurons to those in hippocampal CA1 neurons using the patch clamp technique in brain slice. Glutamate (100 microM) induced an inward current in both SFO and hippocampal CA1 neurons. The density of glutamate-induced current in SFO neurons was significantly smaller than that in hippocampal CA1 neurons (0.55 vs. 2.07 pA/pF, p<0.05). To further identify the subtype of the glutamate receptors involved, the whole cell currents induced by selective agonists were then compared. The current densities induced by AMPA (0.45 pA/pF) and kainate (0.83 pA/pF), non-NMDA glutamate receptor agonists in SFO neurons were also smaller than those in hippocampal CA1 neurons (2.44 pA/pF for AMPA, p<0.05; 2.34 pA/pF for kainate, p< 0.05). However, the current density by NMDA in SFO neurons was not significantly different from that of hippocampal CA1 neurons (1.58 vs. 1.47 pA/pF, p>0.05). These results demonstrate that glutamate-mediated action through non-NMDA glutamate receptors in SFO neurons is smaller than that of hippocampal CA1 neurons, suggesting a possible protection mechanism from excitotoxicity by circulating glutamate in SFO neurons.

Keyword

Circumventricular organs; Excitotoxicity; Hippocampus; Non-NMDA; Slice patch clamp

MeSH Terms

alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
Animals
Blood-Brain Barrier
Brain
Central Nervous System
Glutamic Acid*
Hippocampus
Kainic Acid
N-Methylaspartate
Neurons*
Rats*
Receptors, Glutamate
Subfornical Organ*
Glutamic Acid
Kainic Acid
N-Methylaspartate
Receptors, Glutamate
alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid

Figure

• 

  Fig. 1 Comparison of glutamate-induced inward currents recorded by the slice patch clamp technique in SFO and hippocampal CA1 neurons. (A) Representative traces showing glutamate-induced inward currents on a SFO (left) and a hippocampal CA1 neuron (right), respectively. (B) Comparison of the mean inward currents by glutamate (100 µM) on SFO (n=10) and hippocampal CA1 neurons (n=6). (C) Comparison of the mean current densities by glutamate (100 µM) on SFO and hippocampal CA1 neurons. *represents p<0.05. SFO, Subfornical organ neuron; HP, Hippocampal CA1 neuron.

• 

  Fig. 2 Current responses elicited by non-NMDA receptor agonists (AMPA and kainate) in SFO and hippocampal CA1 neurons in the slice preparation. (A) Representative traces showing currents induced by AMPA (10 µM) and kainate (10 µM) in SFO (left) and hippocampal CA1 neuron (right), respectively. (B, C) Mean amplitude (B) and mean density (C) of inward currents induced by AMPA and kainate in SFO (n=13 and 11) and hippocampal neurons (n=11 and 7) at the peak *p<0.05. SFO, Subfornical organ neuron; HP, Hippocampal CA1 neuron.

• 

  Fig. 3 Current responses elicited by NMDA in SFO and hippocampal neurons. (A) Left and right traces show NMDA (10 µM) induced inward current in SFO and hippocampal CA1 neurons. Mg2+-free ACSF was applied for recording of NMDA induced current. (B, C) Mean inward current induced by NMDA (B) and its mean current density (C) in SFO (n=4) and hippocampalCA1 neurons (n=4). SFO, Subfornical organ neuron; HP, Hippocampal CA1 neuron.

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