Differential effect of zinc on the vertebrate GABAA-receptor complex.
1. gamma-Aminobutyric acid (GABA) responses were recorded from rat superior cervical ganglia (SCG) in culture using the whole cell recording technique. 2. Zinc (50-300 microM) reversibly antagonized the GABA response in embryonic and young post-natal neurones, while neurones cultured from adult animals were far less sensitive and occasionally resistant to zinc blockade. Cadmium (100-300 microM) also antagonised the GABA response, while barium (100 microM-2 mM) was ineffective. 3. The differential blocking effect of zinc on cultured neurones of different ages also occurred in intact SCG tissue. 4. The GABA log dose-response curve constructed with foetal or adult cultured neurones was reduced in a non-competitive manner by zinc. This inhibition was minimally affected by the membrane potential. 5. The GABA response recorded intracellularly from guinea-pig pyriform cortical slices was enhanced by zinc (300-500 microM), which occurred concurrently with a decrease in the input conductance of the cell. The enhancement was unaffected by prior blockade of the GABA uptake carrier by 1 mM nipecotic acid. This phenomenon could be reproduced by barium (300 microM) and cadmium (300 microM). 6. We conclude that the vertebrate neuronal GABAA-receptor becomes less sensitive to zinc with neural (GABAA-receptor?) development, and the enhanced GABA response recorded in the CNS is a consequence of the reduction in the input conductance and not due to a direct effect on the receptor complex.
Smart
T G
TG
Department of Pharmacology, School of Pharmacy, London.
Constanti
A
A
D000375:Aging / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002104:Cadmium / Q000494:pharmacology; D046508:Culture Techniques; D004594:Electrophysiology; D005728:Ganglia, Sympathetic / Q000187:drug effects; D006168:Guinea Pigs; D007478:Iontophoresis; D008564:Membrane Potentials / Q000187:drug effects; D009474:Neurons / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D011963:Receptors, GABA-A / Q000378:metabolism*; D013564:Sympathetic Nervous System / Q000187:drug effects; D015032:Zinc / Q000494:pharmacology*
D011963:Receptors, GABA-A; D002104:Cadmium; D015032:Zinc