Differential effect of zinc on the vertebrate GABA_A‐receptor complex

Abstract

-39 Brunswick Square, London WC1N lAX 1 y-Aminobutyric acid (GABA) responses were recorded from rat superior cervical ganglia (SCG) in culture using the whole cell recording technique.2 Zinc (50-300pM) 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 gM) also antagonised the GABA response, while barium (100 pM-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 (300-500jMm), 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 pM) and cadmium (300 M).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.

Potentiation, activation and blockade of GABAA receptors of clonal murine hypothalamic GT1‐7 neurones by propofol

“…The dose-response relationship for this action of propofol in their preparation looks strikingly similar to that reported here. It may be significant that GABA-responses recorded from embryonic neurones tend to be more sensitive to Zn21 (Smart & Constanti, 1990) and this has been explained by a lack of y subunits Smart et al, 1991). Hence the absence of a y subunit from the GABAA receptor may make propofol less potent and/or efficacious as an activator in GT1-7 cells and embryonic neuronal preparations.…”

“…This regional and developmental heterogeneity may explain reports of variable GABAA receptor modulation by some agents ; Smart & Constanti, 1990;Wafford et al, 1991). Clonal cell lines 'Author for correspondence.…”

“…GABAA receptor subunits are not only differentially distributed between brain regions, , but are also known to vary within neurones at different developmental stages Smart & Constanti, 1990). This regional and developmental heterogeneity may explain reports of variable GABAA receptor modulation by some agents ; Smart & Constanti, 1990;Wafford et al, 1991).…”

Iron, copper, zinc, magnesium, and calcium in postmortem brain tissue from schizophrenic patients

“…Interactions with inhibitory (Smart and Constanti 1990) and excitatory amino acid neurotransmission (Yet et a11990) are well known. Although low to moderate concentrations of zinc attenuate N-methyl-o-aspartate (NMDA)-mediated and enhance quisqualate-mediated neurotoxicity (Koh and Choi 1988), high concentrations of zinc are neurotoxic (Yokoyama et al 1986).…”

Selective Inhibition of Spontaneous But Not Ca2+-Dependent Release Machinery by Presynaptic Group II mGluRs in Rat Cerebellar Slices

“…2C; n ϭ 9). It is well documented in the literature that currents through GABA A receptors are reduced in the presence of Cd 2ϩ (Casagrande et al 2003;Celentano et al 1991;Smart and Constanti 1990). The small reduction in mIPSC frequency observed after addition of Cd 2ϩ (Fig.…”