PMID- 27382359 OWN - NLM STAT- PubMed-not-MEDLINE DCOM- 20160706 LR - 20201001 IS - 1226-4512 (Print) IS - 1226-4512 (Linking) VI - 20 IP - 4 DP - 2016 Jul TI - Facilitation of AMPA receptor-mediated steady-state current by extrasynaptic NMDA receptors in supraoptic magnocellular neurosecretory cells. PG - 425-32 LID - 10.4196/kjpp.2016.20.4.425 [doi] AB - 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 INMDA in various brain regions remains poorly understood. Here, we demonstrate that activation of eNMDARs that generate INMDA facilitates the alpha-amino-3-hydroxy-5-methylisoxazole-4-proprionate receptor (AMPAR)-mediated steady-state current in supraoptic nucleus (SON) magnocellular neurosecretory cells (MNCs). In low-Mg(2+) artificial cerebrospinal fluid (aCSF), glutamate induced an inward shift in Iho lding (IGLU) at a holding potential (Vholding) of -70 mV which was partly blocked by an AMPAR antagonist, NBQX. NBQX-sensitive IGLU was observed even in normal aCSF at Vholding of -40 mV or -20 mV. IGLU was completely abolished by pretreatment with an NMDAR blocker, AP5, under all tested conditions. AMPA induced a reproducible inward shift in Iholding (IAMPA) in SON MNCs. Pretreatment with AP5 attenuated IAMPA amplitudes to ~60% of the control levels in low-Mg(2+) aCSF, but not in normal aCSF at Vholding of -70 mV. IAMPA attenuation by AP5 was also prominent in normal aCSF at depolarized holding potentials. Memantine, an eNMDAR blocker, mimicked the AP5-induced IAMPA attenuation in SON MNCs. Finally, chronic dehydration did not affect IAMPA attenuation by AP5 in the neurons. These results suggest that tonic INMDA, mediated by eNMDAR, facilitates AMPAR function, changing the postsynaptic response to its agonists in normal and osmotically challenged SON MNCs. FAU - Pai, Yoon Hyoung AU - Pai YH AD - Department of Physiology, Brain Research Institute, School of Medicine, Chungnam National University, Daejeon 35015, Korea. FAU - Lim, Chae Seong AU - Lim CS AD - Department of Anesthesiology & Pain Medicine, Brain Research Institute, School of Medicine, Chungnam National University, Daejeon 35015, Korea. FAU - Park, Kyung-Ah AU - Park KA AD - Department of Physiology, Brain Research Institute, School of Medicine, Chungnam National University, Daejeon 35015, Korea. FAU - Cho, Hyun Sil AU - Cho HS AD - Department of Physiology, Brain Research Institute, School of Medicine, Chungnam National University, Daejeon 35015, Korea. FAU - Lee, Gyu-Seung AU - Lee GS AD - Department of Physiology, Brain Research Institute, School of Medicine, Chungnam National University, Daejeon 35015, Korea. FAU - Shin, Yong Sup AU - Shin YS AD - Department of Anesthesiology & Pain Medicine, Brain Research Institute, School of Medicine, Chungnam National University, Daejeon 35015, Korea. FAU - Kim, Hyun-Woo AU - Kim HW AD - Department of Physiology, Brain Research Institute, School of Medicine, Chungnam National University, Daejeon 35015, Korea. FAU - Jeon, Byeong Hwa AU - Jeon BH AD - Department of Physiology, Brain Research Institute, School of Medicine, Chungnam National University, Daejeon 35015, Korea. FAU - Yoon, Seok Hwa AU - Yoon SH AD - Department of Anesthesiology & Pain Medicine, Brain Research Institute, School of Medicine, Chungnam National University, Daejeon 35015, Korea. FAU - Park, Jin Bong AU - Park JB AD - Department of Physiology, Brain Research Institute, School of Medicine, Chungnam National University, Daejeon 35015, Korea. LA - eng PT - Journal Article DEP - 20160623 PL - Korea (South) TA - Korean J Physiol Pharmacol JT - The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology JID - 9709505 PMC - PMC4930911 OTO - NOTNLM OT - AMPA receptors OT - Chronic dehydration OT - Extrasynaptic NMDA receptors OT - Magnocellular neurosecretory cells COIS- CONFLICTS OF INTEREST: The authors declare no conflicts of interest. EDAT- 2016/07/07 06:00 MHDA- 2016/07/07 06:01 PMCR- 2016/07/01 CRDT- 2016/07/07 06:00 PHST- 2016/03/28 00:00 [received] PHST- 2016/06/06 00:00 [revised] PHST- 2016/06/09 00:00 [accepted] PHST- 2016/07/07 06:00 [entrez] PHST- 2016/07/07 06:00 [pubmed] PHST- 2016/07/07 06:01 [medline] PHST- 2016/07/01 00:00 [pmc-release] AID - 10.4196/kjpp.2016.20.4.425 [doi] PST - ppublish SO - Korean J Physiol Pharmacol. 2016 Jul;20(4):425-32. doi: 10.4196/kjpp.2016.20.4.425. Epub 2016 Jun 23.