J Vet Sci.  2018 Mar;19(2):172-178. 10.4142/jvs.2018.19.2.172.

Korean red ginseng excitation of paraventricular nucleus neurons via non-N-methyl-D-aspartate glutamate receptor activation in mice

• Shen Y
• Bhattarai
• Park SJ
• Lee GS
• Ryu PD
• Han SK

• KMID: 2407616
• DOI: http://doi.org/10.4142/jvs.2018.19.2.172

Abstract

It has been reported that Korean red ginseng (KRG), a valuable and important traditional medicine, has varied effects on the central nervous system, suggesting its activities are complicated. The paraventricular nucleus (PVN) neurons of the hypothalamus has a critical role in stress responses and hormone secretions. Although the action mechanisms of KRG on various cells and systems have been reported, the direct membrane effects of KRG on PVN neurons have not been fully described. In this study, the direct membrane effects of KRG on PVN neuronal activity were investigated by using a perforated patch-clamp in ICR mice. In gramicidin perforated patch-clamp mode, KRG extract (KRGE) induced repeatable depolarization followed by hyperpolarization of PVN neurons. The KRGE-induced responses were concentration-dependent and persisted in the presence of tetrodotoxin, a voltage sensitive Na+ channel blocker. The KRGE-induced responses were suppressed by 6-cyano-7-nitroquinoxaline-2,3-dione (10 µM), a non-N-methyl-D-aspartate (NMDA) glutamate receptor antagonist, but not by picrotoxin, a type A gamma-aminobutyric acid receptor antagonist. The results indicate that KRG activates non-NMDA glutamate receptors of PVN neurons in mice, suggesting that KRG may be a candidate for use in regulation of stress responses by controlling autonomic nervous system and hormone secretion.

Keyword

Korean red ginseng; paraventricular nucleus neurons; patch-clamp techniques

MeSH Terms

6-Cyano-7-nitroquinoxaline-2,3-dione
Animals
Autonomic Nervous System
Central Nervous System
Glutamic Acid*
Gramicidin
Hypothalamus
Medicine, Traditional
Membranes
Mice*
Mice, Inbred ICR
Neurons*
Panax*
Paraventricular Hypothalamic Nucleus*
Patch-Clamp Techniques
Picrotoxin
Receptors, GABA
Receptors, Glutamate*
Tetrodotoxin
6-Cyano-7-nitroquinoxaline-2,3-dione
Glutamic Acid
Gramicidin
Picrotoxin
Receptors, GABA
Receptors, Glutamate
Tetrodotoxin

Figure

• 

  Fig. 1 Concentration-dependent Korean red ginseng extract (KRGE) responses on paraventricular nucleus (PVN) neurons. (A) A representative trace from a PVN neuron showing concentration-dependent responses following application of KRGE (0.3, 1.0, and 3.0 mg/mL). Cumulative graphs show the mean membrane depolarization (B) and after-hyperpolarization (C) values after treatment by KRGE (0.3, 1.0, and 3.0 mg/mL). *p < 0.05.

• 

  Fig. 2 Non-desensitizing responses by repeat applications of Korean red ginseng extract (KRGE) on paraventricular nucleus (PVN) neurons. (A) A representative trace from a PVN neuron showing depolarization and after-hyperpolarization after 3.0 mg/mL KRGE application. Mean relative membrane depolarization (B) and after-hyperpolarization (C) by repeat applications of KRGE (3.0 mg/mL). n.s., no significant difference.

• 

  Fig. 3 Korean red ginseng extract (KRGE)-mediated membrane potential changes are induced by direct action on paraventricular nucleus (PVN) neurons. (A) A representative trace from a PVN neuron showing depolarization and after-hyperpolarization by application of 3.0 mg/mL KRGE alone and by KRGE (3.0 mg/mL) with tetrodotoxin (TTX) which blocks action potentials. Mean relative membrane depolarization (B) and after-hyperpolarization (C) by KRGE (3.0 mg/mL) alone and by KRGE (3.0 mg/mL) with TTX. n.s., no significant difference.

• 

  Fig. 4 Korean red ginseng extract (KRGE)-mediated membrane potential changes are mediated by activation of non-N-methyl-D-aspartate (NMDA) receptor glutamate receptors on paraventricular nucleus (PVN) neurons. (A) A representative trace from a PVN neuron showing depolarization and after-hyperpolarization following application of 3.0 mg/mL KRGE alone and KRGE (3.0 mg/mL) with CNQX (6-cyano-7-nitroquinoxaline-2, 3-dione), a non-NMDA glutamate receptor blocker. Mean relative membrane depolarization (B) and after-hyperpolarization (C) by KRGE (3.0 mg/mL) alone and by KRGE (3.0 mg/mL) with CNQX. *p < 0.05.

• 

  Fig. 5 Korean red ginseng extract (KRGE)-mediated membrane potential changes are not mediated by activation of type A gamma-aminobutyric acid (GABAA) receptor on paraventricular nucleus (PVN) neurons. (A) A representative trace from a PVN neuron showing depolarization and after-hyperpolarization following application of KRGE alone (3.0 mg/mL) and KRGE (3.0 mg/mL) with picrotoxin (PIC), a GABAA receptor antagonist. Mean relative membrane depolarization (B) and after-hyperpolarization (C) by KRGE (3.0 mg/mL) and KRGE (3.0 mg/mL) with PIC. n.s., no significant difference.

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