Differential effect of zinc on the vertebrate GABA A ‐receptor complex

1 γ‐Aminobutyric acid (GABA) responses were recorded from rat superior cervical ganglia (SCG) in culture using the whole cell recording technique. 2 Zinc (50–300 μ m ) 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 μ m ) also antagonised the GABA response, while barium (100 μ m ‐2 m m ) 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 μ m ), 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 m m nipecotic acid. This phenomenon could be reproduced by barium (300 μ m ) and cadmium (300 μ m ). 6 We conclude that the vertebrate neuronal GABA A ‐receptor becomes less sensitive to zinc with neural (GABA A ‐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.