Facilitation of AMPA receptor-mediated steady-state current by extrasynaptic NMDA receptors in supraoptic magnocellular neurosecretory cells

다국어 초록 (Multilingual 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 (I_NMDA) 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 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-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 IGLU was observed even in normal aCSF at V_holding 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 (I_AMPA) in SON MNCs. Pretreatment with AP5 attenuated I_AMPA amplitudes to ~60% of the control levels in low-Mg ²⁺ 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 INMDA, mediated by eNMDAR, facilitates AMPAR function, changing the postsynaptic response to its agonists in normal and osmotically challenged SON MNCs.