Differential effect of zinc on the vertebrate GABAA-receptor complex.
Identifieur interne : 000172 ( Ncbi/Merge ); précédent : 000171; suivant : 000173Differential effect of zinc on the vertebrate GABAA-receptor complex.
Auteurs : T. G. Smart ; A. ConstantiSource :
- British Journal of Pharmacology [ 0007-1188 ] ; 1990.
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.
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PubMed: 2163276
PubMed Central: 1917556
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<front><div type="abstract" xml:lang="en"><p>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.</p>
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<front><journal-meta><journal-id journal-id-type="nlm-ta">Br J Pharmacol</journal-id>
<journal-title>British Journal of Pharmacology</journal-title>
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<title-group><article-title>Differential effect of zinc on the vertebrate GABAA-receptor complex.</article-title>
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<contrib-group><contrib contrib-type="author"><name><surname>Smart</surname>
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<aff>Department of Pharmacology, School of Pharmacy, London.</aff>
<pub-date pub-type="ppub"><month>4</month>
<year>1990</year>
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<volume>99</volume>
<issue>4</issue>
<fpage>643</fpage>
<lpage>654</lpage>
<abstract><p>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.</p>
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