title: Facilitation of AMPA receptor-mediated steady-state current by extrasynaptic NMDA receptors in supraoptic magnocellular neurosecretory cells.
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 INMDA in various brain regions remains poorly understood. Here, we demonstrate that activation of eNMDARs that generate INMDA 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-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.
authors.affiliation: Department of Physiology, Brain Research Institute, School of Medicine, Chungnam National University, Daejeon 35015, Korea.
authors.forename: Yoon Hyoung
authors.initials: YH
authors.lastname: Pai
authors.affiliation: Department of Anesthesiology & Pain Medicine, Brain Research Institute, School of Medicine, Chungnam National University, Daejeon 35015, Korea.
authors.forename: Chae Seong
authors.initials: CS
authors.lastname: Lim
authors.affiliation: Department of Physiology, Brain Research Institute, School of Medicine, Chungnam National University, Daejeon 35015, Korea.
authors.forename: Kyung-Ah
authors.initials: KA
authors.lastname: Park
authors.affiliation: Department of Physiology, Brain Research Institute, School of Medicine, Chungnam National University, Daejeon 35015, Korea.
authors.forename: Hyun Sil
authors.initials: HS
authors.lastname: Cho
authors.affiliation: Department of Physiology, Brain Research Institute, School of Medicine, Chungnam National University, Daejeon 35015, Korea.
authors.forename: Gyu-Seung
authors.initials: GS
authors.lastname: Lee
authors.affiliation: Department of Anesthesiology & Pain Medicine, Brain Research Institute, School of Medicine, Chungnam National University, Daejeon 35015, Korea.
authors.forename: Yong Sup
authors.initials: YS
authors.lastname: Shin
authors.affiliation: Department of Physiology, Brain Research Institute, School of Medicine, Chungnam National University, Daejeon 35015, Korea.
authors.forename: Hyun-Woo
authors.initials: HW
authors.lastname: Kim
authors.affiliation: Department of Physiology, Brain Research Institute, School of Medicine, Chungnam National University, Daejeon 35015, Korea.
authors.forename: Byeong Hwa
authors.initials: BH
authors.lastname: Jeon
authors.affiliation: Department of Anesthesiology & Pain Medicine, Brain Research Institute, School of Medicine, Chungnam National University, Daejeon 35015, Korea.
authors.forename: Seok Hwa
authors.initials: SH
authors.lastname: Yoon
authors.affiliation: Department of Physiology, Brain Research Institute, School of Medicine, Chungnam National University, Daejeon 35015, Korea.
authors.forename: Jin Bong
authors.initials: JB
authors.lastname: Park
keywords: AMPA receptors; Chronic dehydration; Extrasynaptic NMDA receptors; Magnocellular neurosecretory cells