The dual effects of GABA and related amino acids on the electrical threshold of ventral horn group Ia afferent terminations in the cat.

Amino acids were administered microelectrophoretically near the unmyelinated terminations of extensor muscle Ia afferent terminations stimulated electrically in the vicinity of lumbar motoneurones in anaesthetized cats. The predominant effect of one group (structurally related to GABA, poor substrates for in vitro amino acid uptake systems) was a reduction in the threshold (depolarization). The second group (including GABA and structural analogues which are substrates for GABA transport systems in vitro) had biphasic effects, an initial reduction being followed by an increase in threshold. The third group (structurally unrelated to GABA, substrates for amino acid uptake systems) only increased Ia termination thresholds. Reductions in termination thresholds, but not increases, were associated with diminution of synaptically evoked primary afferent depolarization, and were decreased by bicuculline methochloride. Many amino acids increased the electrical resistance of the intraspinal medium near the orifices of the barrels of seven barrel micropipettes, and for L-histidine, one of the third group of amino acids, both this effect and the increased threshold of terminations were reversibly modified by microelectrophoretic ouabain. These observations suggest that GABA-mimetics depolarize Ia terminations by interacting with bicuculline-sensitive receptors similar to those at hyperpolarizing gabergic synapses upon spinal interneurones. In addition, under the experimental conditions used, these and other amino acids increase termination thresholds, probably in the absence of any change in membrane conductance, an effect resulting from alterations in the ionic constitution of the extracellular medium around the orifices of micropipettes ejecting amino acids consequent upon the ouabain-sensitive co-transport of amino acids and sodium ions into neurones and glia.