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

Synaptic potentials and the responses of frog spinal cord to various acidic amino acids were examined by means of the sucrose gap recording technique. Divalent cations (50–250 μm) specifically antagonized responses evoked at N‐methyl‐d‐aspartate (NMDA) receptors by N‐methyl d,l aspartic acid (NMDLA). The rank order of potency was Ni2+ > Co≫2+ > Mg2+ > Mn2+. Responses to glutamate and aspartate were relatively insensitive to these concentrations of divalent cations. The rank order of potency for divalent ions (1 mm) for antagonism of synaptic transmission in bullfrog sympathetic ganglia was Mn2+ ≫ Co2+ > Ni2+ ≫ Mg2+. Thus synaptic transmission in ganglia was especially sensitive to Mn2+ whereas NMDLA responses were especially sensitive to Co2+ and Mg2+. It was possible to depress selectively the dorsal root‐dorsal root potential (DR‐DRP) and dorsal root‐ventral root potential (DR‐VRP) of frog spinal cord using low doses of Co2+ or Mg2+ which did not affect VR‐DRP (ventral root‐dorsal root potential). It was not possible to produce this selective depression of DR‐DRP and DR‐VRP with Mn2+, as this cation non‐selectively depressed all responses. These results suggest that: (i) divalent cations do not antagonize NMDLA responses by blocking Ca2+ channels which may mediate the response; (ii) postsynaptic NMD A 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. 1982 British Pharmacological Society