The Use of Low Concentrations of Divalent Cations to Demonstrate a Role for N‐methyl‐d‐aspartate Receptors in Synaptic Transmission in Amphibian Spinal Cord

Abstract

5 These results suggest that: (i) divalent cations do not antagonize NMDLA responses by blocking Ca2+ channels which may mediate the response; (ii) postsynaptic NMDA receptors are activated by a neurotransmitter involved in the DR-DRP and DR-VRP pathways but not by any neurotransmitters involved in the VR-DRP pathway; (iii) the neurotransmitter activating NMDA receptors in amphibian spinal cord may be an aspartate-like substance rather than aspartate itself or glutamate. IntoductionThe acidic amino acids, L-glutamate and L-aspartate, are putative excitatory neurotransmitters in the central nervous system (CNS) (Krnjevic, 1974;Puil, 1981 . Certain lines of evidence support a role for calcium ions in the electrogenesis of responses to acidic amino acids (Sonnhof & Btihrle, 1981;Padjen & Smith, 1981;Puil,1981;butseealso Shapavolov, Shiriaev &Velumain, 1978 and McDonald &Wojtowicz, 1980;. Calcium influx may be especially important for responses evoked by DL-homocysteic acid, an agonist thought to act on NMDA receptors (Heinemann & Pumain, 1981). Recently, Co2+ and Mg2+ have been shown to be selective and highly potent antagonists at NMDA receptors (Ault, Evans, Francis, Oakes & Watkins, 0007-1188/82/100363-11 $01.00 1981). Since these ions are known to block calcium channels (Katz & Miledi, 1967; Alvarez-Leefmans, DeSantis & Miledi, 1979) (Blackman, Ginsborg & Ray, 1963

Comparative actions of gaba and acetylcholine on the Xenopus laevis lateral line

“…Since all three agonists, NMDA, kainate and quisqualate, activate the lateral line (Bledsoe et al, 1983) and their receptors may be activated by L-glutamate, then a portion of the response to L-glutamate in the lateral line is probably due to activation of these receptors. It has been reported that magnesium ions, even in small concentrations, block the NMDA receptor, but not the kainate or quisqualate receptors in other systems (Ault et al, 1980;Smith, 1982). Thus, the block of NMDA we observed with high magnesium was expected.…”

“…Instead, it seems the response to L-glutamate may have been potentiated by the high magnesium. A potentiation of the response to t-glutamate by divalent cations such as magnesium has been reported in other systems (Smith, 1982). This may occur by an action at the remaining kainate and quisqualate receptors.…”

Identification and Characterization of an N‐Methyl‐D‐Aspartate‐Specific L‐[3H]Glutamate Recognition Site in Synaptic Plasma Membranes

“…A likely explanation for this apparent contradiction is that the conditions used by Mena et al ( , 1984 (30°C for 20 min) favored binding to the Ca2+/C1--dependent glutamate binding site, whereas our conditions favor the NMDA site. Relatively low concentrations (50-250 p M ) of cobalt, magnesium, and manganese have been shown to antagonize specifically NMDA-evoked responses in the frog spinal cord (Smith, 1982). Of these ions, cobalt and manganese inhibited NMDA-specific ~-[~H]glutamate binding at a concentration of 1 mM (1 3 and 1 9% inhibition, respectively), whereas magnesium had no effect.…”

Pharmacological aspects of excitatory synaptic transmission to second‐order vestibular neurons in the frog

“…Animals were perfused with Mg++-fi-ee saline prior to decapitation and all recordings were obtained in Mg++-free saline, so that all EPSPs could be fully expressed. Current investigations (Knoepfel, 1986) reveal that Mg+ + in the bath will affect these contralaterally evoked EPSPs in a manner which appears similar to its action in other systems (Ault et al, 1980;Davies and Watkins, 1977;Flatman et al, 1986;Nowak et al, 1984;Smith, 1982). Consequently, the degree of expression of this EPSP in vivo will depend on the Mgf + concentration in the synaptic cleft.…”