ISSN:
1432-1106
Keywords:
Lathyrus neurotoxin
;
Excitatory amino acids
;
Spinal cord neurons
;
Intracellular analysis
;
Ionic mechanisms
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
Summary Intracellular recordings were made in cultured neurones from foetal mouse spinal cord. The effects of applications of the neurotoxin, L-3-oxalylamino-2-amino-propionic acid (a constituent of the chickling pea, Lathyrus sativus) and its 2-oxalyl-amino isome on membrane potential and conductance were examined in the presence of TTX and TEA and compared to those of other excitatory amino acids. Although both compounds produced membrane depolarization and an increase in input conductance, the 3-oxalylamino isomer (β-ODAP) was ≅ 10 times more potent than the 2-oxalylamino isomer (α-ODAP). β-ODAP caused a voltage-independent change in conductance, as compared to an apparent voltage-dependent decrease produced in the same neurons by L-aspartic acid (L-ASP). Although reversal potentials determined for β-ODAP resembled those for α-ODAP and kainic acid, they were consistently and significantly lower than the reversal level for L-ASP. Although the receptor antagonist 2-amino-5-phosphonovaleric acid (APV) and the divalent cation Cd2+ did not alter the conductance increase evoked by β-ODAP, they markedly depressed responses to L-ASP. Such differences suggest a mechanism of excitatory action for the neurotoxin, β-ODAP, which does not involve a Ca2+-dependent mechanism and is quite different from that for L-ASP and N-methyl-D-aspartic acid, but similar to that of kainic and quisqualic acids. It is proposed that excitatory effects of amino acids (e.g. β-ODAP and kainic acid) which involve a voltage-independent mechanism may somewhat paradoxically promote, by means of persistent depolarization, a greater and more toxic accumulation of intracellular Ca2+ than those with a voltage-dependent mechanism (e.g. L-ASP) which activate large oscillations of membrane potential but perhaps more transient influx of Ca2+.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/BF00231142
Permalink