The effect of zinc ions (Zn2+) on the neuronal excitability of substantia nigra (SN) where the zinc level is known higher in Parkinsonian brains than that in normal brains has not yet been elucidated. We, therefore, examined the effect of Zn2+ on the intrinsic electrical properties of dopaminergic SN neurons, using a whole-cell recording method. Zn2+ hyperpolarized dopaminergic SN neurons at resting state. Also Zn2+ shortened the duration of evoked spikes, developed a fast afterhyperpolarization, and increased their firing frequency. Voltage-clamp studies showed that Zn2+ decreased 4-aminopyridine-sensitive outward currents, suggesting that a transient A-like potassium channel be one of the major targets Zn2+ can modulate in the SN neurons. (C) 2000 Elsevier Science Ireland Ltd.