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

Abstract

The effect of Zn2+ on a voltage-dependent, transient potassium current (IA) in acutely dissociated neurons from the suprachiasmatic nucleus was studied with the whole-cell patch-clamp technique. At micromolar concentrations, Zn2+ markedly potentiated IA 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 microM and increased with higher Zn2+ concentrations. The Zn2+ action appears to arise from a shift in the steady-state inactivation of IA to more positive voltages. At 30 microM, Zn2+ shifted the half-inactivation voltage by +20 mV (from -80 mV to -60 mV), and 200 microM 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 IA. Because vesicular Zn2+ is fairly widespread in the central nervous system, it is conceivable that this kind of Zn2+ modulation on IA, and possibly on other voltage-activated currents, exists elsewhere in the brain.