Age‐related functional changes of the glutamate receptor channels in rat Meynert neurones

Abstract

The developmental changes of glutamate receptors (GluRs) in acutely dissociated rat Meynert neurones were investigated using the conventional whole‐cell and nystatin perforated patch recording modes under voltage‐clamp conditions. The neurones became less responsive to N‐methyl‐d‐aspartic acid (NMDA) with age, most dramatically between 1 day and 2 weeks, while the responses to kainic acid (KA) and l‐α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid (AMPA) gradually increased. The metabotropic GluR response appeared a few days after birth, but thereafter no further change was observed. The decrease in the NMDA response during postnatal development was due to an abrupt reduction in the number of receptors without affecting the affinity, voltage‐dependent Mg2+ blockade or high Ca2+ permeability (Pca/PCs≈ 7.0). P ca/PCs in the presence of KA decreased from 2.8 in the 1‐day‐old (1D) rat neurones to 1.1 and 0.44 in the 2‐week‐old (2W) and 6‐month‐old (6M) rat neurones, respectively. The concentration–response relationship for KA shifted to the left with age. The KA response was not affected by NS‐102, a KA‐selective antagonist, thus indicating that the increased affinity of the receptor for the ligand resulted from the change in the AMPA receptor channel subunits. The AMPA response in the presence of 10−4 M cyclothiazide showed a change in the inward rectifying current–voltage relationship with age. The KA response was strongly cross‐desensitized by the addition of AMPA and was also blocked by 6‐cyano‐7‐nitroquinoxaline‐2,3‐dione (CNQX), whereas a rapid desensitization of the AMPA response was removed in a concentration‐dependent manner by cyclothiazide. These results indicate that the non‐NMDA receptor channels are assembled from the subunits of the AMPA receptor family without the GluR‐2 subunit, thus resulting in a high Ca2+ permeability. The l‐glutamate (Glu)‐induced responses were more sensitive to dl‐2‐amino‐5‐phosphonopentanoic acid (APV) in the 1D rat neurones than in the adult rat neurones. Both NMDA and KA raised the intracellular Ca2+ concentration ([Ca2+]i) in all neurones of 1D, 2W and 6M rats, though the charybdotoxin‐sensitive Ca2+‐activated K+ current (IK(ca)) did not appear in the 1D rat neurones. An age‐related prolongation of both IK(Ca) decay and [Ca2+]i clearance was also seen after the removal of KA. It was thus concluded that the age‐related changes of ionotropic receptors appear to play a key role in the activities of immature and mature rat Meynert cholinergic neurones. The KA‐induced IK(Ca), which developed with ageing, may thus function as one of the negative feedback systems, and thereby prevent excess cell excitation and neural damage, especially in adult rats.

Modifications of excitatory and inhibitory transmission in rat hippocampal pyramidal neurons by acute lithium treatment

“…The Na + /Li + permeability ratio in the myelinated nerve fibers of frogs is 0.93 (Hille, 1972). In the present study, I Glu recorded from CA3 cell body was fully sensitive to CNQX, suggesting a contribution from AMPA/KA receptors due to their having large cation channels but not NMDA receptors (Isa et al,1996;Akaike and Rhee, 1997). The inhibition of I Glu in the 90 and 150 mM Li + mediums was significant, though the inhibition was less than 8% and 17%, respectively (Fig.…”

Expression of Functional Metabotropic Glutamate Receptors in Primary Cultured Rat Osteoblasts

“…The discovery of functional, PLClinked mGluRs in osteoblasts indicates that glutamate signaling may exert complex effects on the regulation of bone cells. Firstly, the receptor cross-talk that we describe here will be of significance in regulating the effect of glutamate signaling and may itself be developmentally regulated by selective expression of different NMDAR-2 s, as has been described in the brain (26,37,44,45). Interestingly, it appears that negative modulation of NMDA receptors by mGluRs does not occur in cultured osteoclasts, because the NMDA receptor currents evoked in these cells by L-glutamate and NMDA are similar (12,14).…”

Attenuation of Acute Morphine Withdrawal in the Neonatal Rat by the Competitive NMDA Receptor Antagonist LY235959

“…More importantly, the NMDA receptor, which is believed to play a crucial role in the establishment of opiate dependence, undergoes qualitative and quantitative changes during development (Kalb et al 1992;Hori and Kanda 1994;Kalb and Fox 1997). These include significant developmental alterations both in the density of the receptor (Tremblay et al 1988;Morin et al 1989;Represa et al 1989), the sensitivity of the receptor complex to magnesium Bowe and Nadler 1990;Morrisett et al 1990), and the rise and decay times of the NMDA receptor-mediated excitatory post-synaptic currents (EPSCs) (Akaike and Rhee 1997;Bardoni et al 1998). Recently, due to the advancement in cloning technology and gene knockout technology, the molecular structure of the NMDA receptor complex has been characterized (Ozawa et al 1998;Dingledine et al 1999).…”