Low Non-NMDA Receptor Current Density as Possible Protection Mechanism from Neurotoxicity of Circulating Glutamate on Subfornical Organ Neurons in Rats.
The subfornical organ (SFO) is one of circumventricular organs characterized by the lack of a normal blood brain barrier. The SFO neurons are exposed to circulating glutamate (60~100 µM), which may cause excitotoxicity in the central nervous system. However, it remains unclear how SFO neurons are protected from excitotoxicity caused by circulating glutamate. In this study, we compared the glutamate-induced whole cell currents in SFO neurons to those in hippocampal CA1 neurons using the patch clamp technique in brain slice. Glutamate (100 µM) induced an inward current in both SFO and hippocampal CA1 neurons. The density of glutamate-induced current in SFO neurons was significantly smaller than that in hippocampal CA1 neurons (0.55 vs. 2.07 pA/pF, p<0.05). To further identify the subtype of the glutamate receptors involved, the whole cell currents induced by selective agonists were then compared. The current densities induced by AMPA (0.45 pA/pF) and kainate (0.83 pA/pF), non-NMDA glutamate receptor agonists in SFO neurons were also smaller than those in hippocampal CA1 neurons (2.44 pA/pF for AMPA, p<0.05; 2.34 pA/pF for kainate, p< 0.05). However, the current density by NMDA in SFO neurons was not significantly different from that of hippocampal CA1 neurons (1.58 vs. 1.47 pA/pF, p>0.05). These results demonstrate that glutamate-mediated action through non-NMDA glutamate receptors in SFO neurons is smaller than that of hippocampal CA1 neurons, suggesting a possible protection mechanism from excitotoxicity by circulating glutamate in SFO neurons.
Department of Veterinary Pharmacology, College of Veterinary Medicine, Seoul National University, Seoul 151-742, Korea.
Wonee
W
Chong
Department of Veterinary Pharmacology, College of Veterinary Medicine, Seoul National University, Seoul 151-742, Korea.
Seong Nam
SN
Kim
Department of Oral Physiology, School of Dentistry and Institute of Oral Bioscience, Chonbuk National University, Jeonju 561-756, Korea.
Seong Kyu
SK
Han
Department of Veterinary Pharmacology, College of Veterinary Medicine, Seoul National University, Seoul 151-742, Korea.
So Yeong
SY
Lee
Department of Veterinary Pharmacology, College of Veterinary Medicine, Seoul National University, Seoul 151-742, Korea.
Pan Dong
PD
Ryu
Circumventricular organs; Excitotoxicity; Hippocampus; Non-NMDA; Slice patch clamp