Zinc modulation of a transient potassium current and histochemical localization of the metal in neurons of the suprachiasmatic nucleus

The effect of Zn²⁺ on a voltage-dependent, transient potassium current (I_A) in acutely dissociated neurons from the suprachiasmatic nucleus was studied with the whole-cell patch-clamp technique. At micromolar concentrations, Zn²⁺ markedly potentiated I_A activated from a holding potential of -60 mV, which is the resting potential of these neurons. This potentiation occurred at a Zn²⁺ concentration as low as 2 μM and increased with higher Zn²⁺ concentrations. The Zn²⁺ action appears to arise from a shift in the steady-state inactivation of I_A to more positive voltages. At 30 μM, Zn²⁺ shifted the half-inactivation voltage by +20 mV (from -80 mV to -60 mV), and 200 μM Zn²⁺ shifted this voltage by +45 mV (from -80 mV to -35 mV). Histochemically, we have also observed Zn²⁺ staining throughout the suprachiasmatic nucleus; the staining is particularly intense in the ventrolateral region of the nucleus, which receives the major fiber inputs. Our findings suggest that Zn²⁺, presumably synaptically released, may modulate the electrical activity of suprachiasmatic nucleus neurons through I_A. Because vesicular Zn²⁺ is fairly widespread in the central nervous system, it is conceivable that this kind of Zn²⁺ modulation on I_A, and possibly on other voltage-activated currents, exists elsewhere in the brain.