Multiple mechanisms of antagonism ofγ-aminobutyric acid (GABA) responses
Gamma-aminobutyric acid (GABA) is one of the most important neurotransmitters in the brain. In an effort to understand the operation of the GABA receptor-ionophore complex, the antagonism of GABA responses by four substances was studied in bullfrog dorsal root ganglion cells by concentration-clamp and internal-perfusion techniques.
Two antagonists (bicuculline and Zn2+) were competitive; two (picrotoxin and penicillin) were noncompetitive. However, significant changes in the kinetics of activation and inactivation were produced by the antagonists, including those that were competitive.
The causes of these changes may be important clues to the structure and operation of the GABA receptor-ionophore complex.
Key wordsγ-aminobutyric acid (GABA) dorsal root ganglion neurons internal perfusion GABA antagonists
Unable to display preview. Download preview PDF.
- Akaike, N., Hattori, K., Oomura, Y., and Carpenter, D. O. (1985). Bicuculline and picrotoxin blockγ-aminobutyric acid-gated Cl− conductance by different mechanisms.Experientia 4170–71.Google Scholar
- Akaike, N., Inone, M., and Kristal, O. A. (1986). “Concentration clamp” study ofγ-aminobutyric acid-induced chloride current kinetics in frog sensory neurons.J. Physiol. (Lond.)379171–185.Google Scholar
- Barker, J. L., and Ransom, B. R. (1978). Amino acid pharmacology of mammalian central neurons grown in tissue culture.J. Physiol. (Lond.)280331–354.Google Scholar
- Brookes, N., and Werman, R. (1973). The cooperativity ofγ-aminobutyric acid action on the membrane of locust muscle fibers.Mol. Pharmacol. 9571–579.Google Scholar
- Carpenter, D. O., Greene, L. A., Shain, W., and Vogel, Z. (1976). Effects of eserine and neostigmine on the interaction ofα-bungarotoxin withAplysia acetylcholine receptors.Mol. Pharmacol. 12999–1006.Google Scholar
- Feltz, A., and Trautman, A. (1982). Desensitization at the frog neuromuscular junction: A biphasic process.J. Physiol. (Lond.)322257–272.Google Scholar
- Gallagher, J. P., Higashi, H., and Nishi, S. (1978). Characterization and ionic basis of GABA-induced depolarizations recordedin vitro from cat primary afferent neurons.J. Physiol. (Lond.)275263–282.Google Scholar
- Hattori, K., Akaike, N., Oomura, Y., and Kuraoka, S. (1984). Separation of GABA-induced chloride current in the frog primary afferent neuron.Am. J. Physiol. 246C259-C265.Google Scholar
- Hochner, B., Spira, M. E., and Werman, R. (1976). Penicillin decreases chloride conductance in crustacean muscle.Brain Res. 10785–103.Google Scholar
- Lebeda, F. J., Hablitz, J. J., and Johnston, D. (1982). Antagonism of GABA-mediated responses by d-tubocurarine in hippocampal neurons.J. Neurophysiol. 48622–632.Google Scholar
- McGeer, P. L., and McGeer, E. G. (1981). Amino acid neurotransmitters. InBasic Neurochemistry (Siegel, G. J., Albers, R. W., Agranoff, B. W., and Kutzman, R., Eds.), Little, Brown, Boston, pp. 233–253.Google Scholar
- Pellmar, T. C., and Wilson, W. A. (1977). Penicillin effects on iontophoretic responses inAplysia californica.Brain Res. 13689–101.Google Scholar
- Ribak, C. E., Harris, A. B., Vaughn, J. E., and Roberts, E. (1981). Immunocytochemical changes in cortical GABA neurons in a monkey model of epilepsy. InNeurotransmitters, Seizures and Epilepsy (Morselli, P. L., Lloyd, K. G., Loscher, W., Meldrum, B., and Reynolds, E. H., Eds.), Raven Press, New York, pp. 11–22.Google Scholar
- Slater, N. T., Hall, A. F., and Carpenter, D. O. (1984). Kinetic properties of cholinergic desensitization inAplysia neurons.Proc. R. Soc. Lond. B23363–78.Google Scholar
- Slater, N. T., Hall, A. F., and Carpenter, D. O. (1985). Trifluoperazine and calcium antagonists accelerate cholinergic desensitization inAplysia neurons.Brain Res. 329275–278.Google Scholar
- Slater, N. T., Filbert, M., and Carpenter, D. O. (1986). Multiple interaction of acetylcholinesterases withAplysia acetylcholine responses.Brain Res. 375407–412.Google Scholar