Facilitation of AMPA receptor-mediated steady-state current by extrasynaptic NMDA receptors in supraoptic magnocellular neurosecretory cells.
10.4196/kjpp.2016.20.4.425
- Author:
Yoon Hyoung PAI
1
;
Chae Seong LIM
;
Kyung Ah PARK
;
Hyun Sil CHO
;
Gyu Seung LEE
;
Yong Sup SHIN
;
Hyun Woo KIM
;
Byeong Hwa JEON
;
Seok Hwa YOON
;
Jin Bong PARK
Author Information
1. Department of Physiology, Brain Research Institute, School of Medicine, Chungnam National University, Daejeon 35015, Korea. jinbong@cnu.ac.kr seohwy@cnu.ac.kr
- Publication Type:Original Article
- Keywords:
AMPA receptors;
Chronic dehydration;
Extrasynaptic NMDA receptors;
Magnocellular neurosecretory cells
- MeSH:
alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid*;
Brain;
Cerebrospinal Fluid;
Dehydration;
Glutamic Acid;
Memantine;
N-Methylaspartate*;
Neurons;
Receptors, AMPA;
Receptors, N-Methyl-D-Aspartate*;
Supraoptic Nucleus;
Synaptic Transmission
- From:The Korean Journal of Physiology and Pharmacology
2016;20(4):425-432
- CountryRepublic of Korea
- Language:English
-
Abstract:
In addition to classical synaptic transmission, information is transmitted between cells via the activation of extrasynaptic receptors that generate persistent tonic current in the brain. While growing evidence supports the presence of tonic NMDA current (INMDA) generated by extrasynaptic NMDA receptors (eNMDARs), the functional significance of tonic I(NMDA) in various brain regions remains poorly understood. Here, we demonstrate that activation of eNMDARs that generate I(NMDA) facilitates the α-amino-3-hydroxy-5-methylisoxazole-4-proprionate receptor (AMPAR)-mediated steady-state current in supraoptic nucleus (SON) magnocellular neurosecretory cells (MNCs). In low-Mg2+ artificial cerebrospinal fluid (aCSF), glutamate induced an inward shift in I(holding) (I(GLU)) at a holding potential (V(holding)) of -70 mV which was partly blocked by an AMPAR antagonist, NBQX. NBQX-sensitive I(GLU) was observed even in normal aCSF at V(holding) of -40 mV or -20 mV. I(GLU) was completely abolished by pretreatment with an NMDAR blocker, AP5, under all tested conditions. AMPA induced a reproducible inward shift in I(holding) (I(AMPA)) in SON MNCs. Pretreatment with AP5 attenuated I(AMPA) amplitudes to ~60% of the control levels in low-Mg2+ aCSF, but not in normal aCSF at V(holding) of -70 mV. I(AMPA) attenuation by AP5 was also prominent in normal aCSF at depolarized holding potentials. Memantine, an eNMDAR blocker, mimicked the AP5-induced I(AMPA) attenuation in SON MNCs. Finally, chronic dehydration did not affect I(AMPA) attenuation by AP5 in the neurons. These results suggest that tonic I(NMDA), mediated by eNMDAR, facilitates AMPAR function, changing the postsynaptic response to its agonists in normal and osmotically challenged SON MNCs.
