Zinc modulation of ionic currents in the horizontal limb of the diagonal band of Broca

We examined modulation of ionic currents by Zn2+ in acutely dissociated neurons from the rat's horizontal limb of the diagonal band of Broca using the whole-cell patch-clamp technique. Application of 50μM Zn2+ increased the peak amplitude of the transiently activated potassium current, IA (at +30mV), from 2.20±0.08 to 2.57±0.11nA (n=27). This response was reversible and could be repeated in 0 Ca2+/1μM tetrodotoxin (n=15). Zn2+ shifted the inactivation curve to the right, resulting in a shift in the half-inactivation voltage from −76.4±2.2 to −53.4±2.0mV (n=11), with no effect on the voltage dependence of activation gating (n=15). There was no significant difference in the time to peak under control conditions (7.43±0.35ms, n=14) and in the presence of Zn2+ (8.20±0.57ms, n=14). Similarly, the time constant of decay of IA (τd) at +30mV showed no difference (control: 38.68±3.68ms, n=15; Zn2+: 38.48±2.85ms, n=15). IA was blocked by 0.5–1mM 4-aminopyridine. In contrast to its effects on IA, Zn2+ reduced the amplitude of the delayed rectifier potassium current (IK). The reduction of outward K+ currents was reproducible when cells were perfused with 1μM tetrodotoxin in a 0 Ca2+ external solution. The amplitude of the steady-state outward currents at +30mV under these conditions was reduced from 6.40±0.23 (control) to 5.76±0.18nA in the presence of Zn2+ (n=16). The amplitudes of peak sodium currents (INa) were not significantly influenced (n=10), whereas barium currents (IBa) passing through calcium channels were potently modulated. Zn2+ reversibly reduced IBa at −10mV by ∼85% from −2.06±0.14nA under control conditions to −0.30±0.10nA in the presence of Zn2+ (n=14). Further analyses of Zn2+ effects on specific calcium channels reveals that it suppresses all types of high-voltage-activated Ca2+ currents.