Conductance increases produced by glycine and gamma-aminobutyric acid in lamprey interneurones.

1. Conductances of individual neurones in the isolated lamprey spinal cord were measured with separate intracellular electrodes for recording potentials and for passing current pulses during application of glycine or GABA (0.1-1.0 MM) in Ca-free bathing fluid. Large, reversible increases in conductance were produced in giant interneurones by both amino acids, but Müller axons and sensory dorsal cells were unaffected. 2. Conductance increases produced by glycine and by GABA were selective for Cl. Both conductance increases were linearly related to external Cl concentrations and repeated exposure to the amino acids in Cl-free fluid progressively reduced the conductance increases to less than 1% of their values in normal Cl. 3. Strychnine was a competitive antagonist of glycine, while GABA was antagonized competitively by bicuculline and non-competitively by picrotoxin. 4. The sensitivity of giant interneurones to glycine and GABA increased at low temperatures, in Na-free fluid, and after repeated exposure to the amino acids. Sensitization may have been produced by inhibition of uptake mechanisms for glycine and GABA in the spinal cord. 5. Discharges of interneurones recorded extracellularly were inhibited by bath-applied glycine and GABA, but directly elicited action potentials of axons were unaffected. Strychnine and Cl-free fluid in the presence of Ca produced seizures in lamprey spinal cord. 6. The conclusions of these experiments are that different receptors for glycine and for GABA are present on giant interneurones, that glycine is the better candidate for an inhibitory transmitter in the lamprey spinal cord, and that GABA produces effects similar to those which have been well studied in arthropod muscle.