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Laboratory of Developmental Neurobiology, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland, and the Department of Neurology, University of Virginia School of Medicine, Charlottesville, Virginia (Dr. Macdonald); and the Laboratory of Neurophysiology, National Institute of Neurological and Communicative Disorders and Stroke, Bethesda, Maryland (Dr. Barker).
Mammalian spinal neurons grown in tissue culture were used to study the effects of the four convulsants—penicillin, pentylenetetrazol, picrotoxin, and bicuculline—on these neurons responses to amino acids. Bath application of all four convulsants produced paroxysmal depolarizing events in the neurons; iontophoresis of the four convulsants selectively depressed responses produced by iontophoresis of the putative inhibitory transmitter GABA, and effected this depression without altering either inhibitory responses to ß-alanine or glycine, or excitation mediated by glutamate. These results support the hypothesis that the convulsant activity of these agents comes in part from selective antagonism of GABA-mediated postsynaptic inhibition.
Dr. Macdonald's address is Laboratory of Developmental Neurobiology, NICHD-NIH, Bldg. 36, Rm. 2A21, Bethesda, MD 20014.
Presented in part at the twenty-ninth annual meeting of the American Academy of Neurology, Atlanta, Georgia, April 1977.
Accepted for publication November 9, 1977.
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C Braestrup, R Schmiechen, G Neef, M Nielsen, and E. Petersen Interaction of convulsive ligands with benzodiazepine receptors Science, June 11, 1982; 216(4551): 1241 - 1243. [Abstract] [PDF]
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J. Barker and D. Mathers GABA analogues activate channels of different duration on cultured mouse spinal neurons Science, April 17, 1981; 212(4492): 358 - 361. [Abstract] [PDF]
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J. Barker and J. MacDonald Picrotoxin convulsions involve synaptic and nonsynaptic mechanisms on cultured mouse spinal neurons Science, May 30, 1980; 208(4447): 1054 - 1056. [Abstract] [PDF]
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R. Wong and D. Prince Dendritic mechanisms underlying penicillin-induced epileptiform activity Science, June 15, 1979; 204(4398): 1228 - 1231. [Abstract] [PDF]
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R. Macdonald and J. Barker Different actions of anticonvulsant and anesthetic barbiturates revealed by use of cultured mammalian neurons Science, May 19, 1978; 200(4343): 775 - 777. [Abstract] [PDF]
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