Zinc modulation of ionic currents in the horizontal lime of the diagonal band of Broca
Zinc modulation of ionic currents in the horizontal lime of the diagonal band of Broca
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DOI：
10.1016/s0306-4522(99)00308-5
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发表时间：
1999-01-01
期刊：
影响因子：
3.3
通讯作者：
Jhamandas, JH
中科院分区：
文献类型：
--
作者：
Easaw, JC;Jassar, BS;Jhamandas, JH
我们研究调制离子电流的Zn 2+在急性分离的神经元从大鼠的水平肢体的斜角带的Broca使用全细胞膜片钳技术。应用50 μ M Zn ~（2+）使瞬时激活钾电流的峰值幅度（I-A）（+ 30 mV）从2.20 ± 0.08增加到2.57 ± 0.11 nA（n = 27）。这种反应是可逆的，并可在0 Ca ~（2+）/1 μ M河豚毒素中重复（n = 15）。Zn 2+使失活曲线向右移动，导致半失活电压从-76.4 +/- 2.2移动到-53.4 +/- 2.0 mV（n = 11），对激活门控的电压依赖性没有影响（n = 15）。在对照条件下（7.43 +/- 0.35 ms，n = 14）和存在Zn 2+时（8.20 +/- 0.57 ms，n = 14），达到峰值的时间无显著差异。同样，在+30 mV下I-A（tau（d））的衰减时间常数没有显示出差异（对照：38.68 +/- 3.68 ms，n = 15; Zn 2+：38.48 +/- 2.85 ms，n = 15）。I-A被0.5-ImM 4-氨基吡啶阻断。与其对I-A的影响相反，Zn ~（2+）降低延迟整流钾电流（I-K）的幅度。当细胞在0 Ca ~（2+）的外部溶液中灌注1 μ M河豚毒素时，外向K ~+电流的降低是可重复的。在这些条件下，在+30 mV下的稳态外向电流的幅度从6.40 +/- 0.23（对照）降低到5.76 +/- 0.18 nA，在Zn 2+（n = 16）的存在下。峰值钠电流（I-Na）的幅度没有受到显著影响（n = 10），而通过钙通道的钡电流（I-Ba）受到有力的调制。在-10 mV下，Zn 2+可逆地将I-Ba从对照条件下的-2.06 +/- 0.14 nA还原至Zn 2+存在下的-0.30 +/- 0.10 nA，还原率接近85%（n = 14）。进一步分析Zn ~（2+）对特异性钙通道的作用发现，Zn ~（2+）抑制所有类型的高压激活的Ca ~（2+）电流，在电流钳条件下，Zn ~（2+）的应用导致兴奋性增加和调节丧失（n = 13），这似乎是通过其对Ca ~（2+）依赖性电导的影响介导的。(C)1999年IBRO。出版社：Elsevier Science Ltd
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 50 mu M Zn2+ 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 Ca2+/1 mu M 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 +/- 2.0 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 Zn2+ (8.20 +/- 0.57 ms, n = 14). Similarly, the time constant of decay of I-A (tau(d)) at + 30 mV showed no difference (control: 38.68 +/- 3.68 ms, n = 15; Zn2+: 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, Zn2+ 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 mu M tetrodotoxin in a 0 Ca2+ 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 Zn2+ (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. Zn2+ reversibly reduced I-Ba at - 10 mV by similar to 85% from - 2.06 +/- 0.14 nA under control conditions to - 0.30 +/- 0.10 nA 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.Under current-clamp conditions, application of Zn2+ resulted in an increase in excitability and loss of accommodation (n = 13), which appears to be mediated through its effects on Ca2+-dependent conductances. (C) 1999 IBRO. Published by Elsevier Science Ltd.