Copper activates a unique inward current in molluscan neurones.

1. Reidentifiable Aplysia neurones were current and voltage clamped in vitro using standard microelectrode techniques. 2. Bath or focal application of Cu2+ at concentrations of 1-100 microM produced a rapid and reversible depolarization of the somal, but not the axonal, membrane potential. The depolarization was accompanied by an increased membrane conductance and activation of an inward current (ICu) which could not be activated by intracellular ionophoretic injection of Cu2+. 3. ICu is carried, in part, by Na+ because the reversal potential of ICu was shifted in a Nernstian fashion by decreasing the extracellular Na+ concentration. The reversal potential of ICu was not affected by removal of extracellular Ca2+ or K+. 4. ICu does not result from (1) activation of known chemically or voltage-gated Na+ conductances, (2) inhibition of the Na+-K+-ATPase or (3) a generalized increase in membrane permeability resulting from lipid peroxidation. 5. A similar inward current was activated by AgNO3 (100 microM) and HgCl2 (100 microM).