Differential effect of zinc on the vertebrate GABAA-receptor complex.

Smart, T.G. and Constanti, A. (1990) Differential effect of zinc on the vertebrate GABAA-receptor complex. British Journal of Pharmacology, 99 (4). pp. 643-654.

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Official URL: http://www.ukpmc.ac.uk/articles/PMC1917556

Abstract

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.

Item Type:Article
Departments, units and centres:Department of Pharmacology > Department of Pharmacology
ID Code:2533
Journal or Publication Title:British Journal of Pharmacology
Deposited By:Library Staff
Deposited On:25 Nov 2011 10:00
Last Modified:25 Nov 2011 10:00

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