Cu2+ Suppresses GABAA Receptor-Mediated Responses in Rat Sacral Dorsal Commissural Neurons

Abstract

The effect of copper ions (Cu²⁺) on γ-aminobutyric acid (GABA)-induced responses in acutely dissociated neurons from the rat sacral dorsal commissural nucleus (SDCN) was investigated using a nystatin-perforated patch recording configuration under voltage clamp conditions. The application of Cu²⁺ to SDCN neurons reversibly suppressed the GABA (10 µM)-activated Cl^– current (I_GABA) in a concentration-dependent manner (1–1,000 µM; IC₅₀ = 24.5 µM). In the presence of Cu²⁺ (30 µM), the concentration-response curve of GABA was shifted rightward without reducing I_GABA recorded under the maximally effective concentration of GABA, thus indicating a dependence of Cu²⁺ action on GABA concentration. Inhibition of GABA (10 µM) responses by 30 µM Cu²⁺ was essentially voltage independent and was not accompanied by a shift in the reversal potential of the currents. Cu²⁺ antagonized the suppressive effect of Zn²⁺ in a concentration-dependent manner, suggesting competition between Cu²⁺ and Zn²⁺ for similar binding sites. These data demonstrate that Cu²⁺ is a potent inhibitor of GABA_A receptor-mediated responses, implying a possible modulatory effect of Cu²⁺ on GABAergic synaptic transmission in the mammalian SDCN.