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

1 Synaptic potentials and the responses of frog spinal cord to various acidic amino acids were examined by means of the sucrose gap recording technique. 2 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. 3 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⁺. 4 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. 5 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.