Journal club: An increased extrasynaptic NMDA tone inhibits A-type K+ current and increases excitability of hypothalamic neurosecretory neurons in hypertensive rats.

by Meng Zhang, Vinicia C. Bianchardi and Javier E. Stern
DOI: 10.1113/JP274327

In this paper the authors tried to elucidate the mechanism of how the magnocellular neurosecretory neurons become hyperexcitable under pathological condition that could lead to high blood pressure and heart failure.

   Magnocellular neurosecretory cells (MNCs) in hypothalamus release vasopressin and oxytocin, which control fluid balance, and cardio-vascular and reproductive homeostasis. The MNC activity is fine-tuned by intrinsic membrane property, by extrasynaptic inputs, and by the activity of neighbouring astrocytes. MNCs have A-current, which pulls down MNCs from firing action potentials.
   In this study, the authors showed that the activation of eNMDARs inhibited A-current in sham MNCs, but not in MNCs from renovascular hypertensive (RVH) rats. However, neither the exogenously evoked NMDA current nor the expression of NMDAR subunits were altered in RVH rats.  Instead, a larger endogenous glutamate tone, which was not due to blunted glutamate transport activity, led to the sustained activation of eNMDARs. This tonically inhibited A-current and contributed in turn to higher firing activity in RVH rats.

   In this study, they did not show the inactivation curve for the A-current. If I were a referee, I would ask them to show it, because the Glu tone should act very slowly. A-current can inactivated under such condition.

   So, the basal Glu level appears to be very important in regulating the homeostatic functions. It might not be just in the brain. If the extrasynaptic GluRs play similar roles in other nervous system, I can speculate that chronic consumption of MSG might have some bad effects on the peripheral nervous systems such as those controlling guts.