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

We examined modulation of ionic currents by Zn 2+ 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 50 μM Zn 2+ increased the peak amplitude of the transiently activated potassium current, I A (at +30 mV), from 2.20±0.08 to 2.57±0.11 nA ( n=27). This response was reversible and could be repeated in 0 Ca 2+/1 μM tetrodotoxin ( n=15). Zn 2+ shifted the inactivation curve to the right, resulting in a shift in the half-inactivation voltage from −76.4±2.2 to −53.4±2.0 mV ( 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±0.35 ms, n=14) and in the presence of Zn 2+ (8.20±0.57 ms, n=14). Similarly, the time constant of decay of I A (τ d) at +30 mV showed no difference (control: 38.68±3.68 ms, n=15; Zn 2+: 38.48±2.85 ms, n=15). I A was blocked by 0.5–1 mM 4-aminopyridine. In contrast to its effects on I A, Zn 2+ reduced the amplitude of the delayed rectifier potassium current ( I K). The reduction of outward K + currents was reproducible when cells were perfused with 1 μM tetrodotoxin in a 0 Ca 2+ external solution. The amplitude of the steady-state outward currents at +30 mV under these conditions was reduced from 6.40±0.23 (control) to 5.76±0.18 nA in the presence of Zn 2+ ( n=16). The amplitudes of peak sodium currents ( I Na) were not significantly influenced ( n=10), whereas barium currents ( I Ba) passing through calcium channels were potently modulated. Zn 2+ reversibly reduced I Ba at −10 mV by ∼85% from −2.06±0.14 nA under control conditions to −0.30±0.10 nA in the presence of Zn 2+ ( n=14). Further analyses of Zn 2+ effects on specific calcium channels reveals that it suppresses all types of high-voltage-activated Ca 2+ currents. Under current-clamp conditions, application of Zn 2+ resulted in an increase in excitability and loss of accommodation ( n=13), which appears to be mediated through its effects on Ca 2+-dependent conductances.