Mg²⁺ decreased basal and GABA-inhibited
t-butylbicyclophosphoro[³⁵S]thionate binding to GABA_A receptor ion
channels in rat brain sections up to 1 mM, but increased the binding at
10 mM. The Mg²⁺-effect was detectable in the presence of a specific GABA
site competitive antagonist. Two-electrode voltage clamp recordings of
recombinant alpha1beta2gamma2S, alpha1beta2, alpha2beta2gamma2S and
alpha2beta2 GABA_A receptors revealed a potentiation by 0.1-1 mM Mg²⁺ of
EC₂₀ GABA-evoked ion currents. At 10 mM, Mg²⁺ decreased the currents. In
the absence of GABA, Mg²⁺ did not evoke any currents. The results show
that physiologically relevant Mg²⁺ concentrations affect the GABA
responses on GABA_A receptors in native and the main recombinant receptor
subtypes, suggesting putative Mg²⁺ binding sites on the receptor
complex.