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首页> 外文期刊>Journal of Neurophysiology >Extracellular inhibition and intracellular enhancement of Ca2+ currents by Pb2+ in bovine adrenal chromaffin cells.
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Extracellular inhibition and intracellular enhancement of Ca2+ currents by Pb2+ in bovine adrenal chromaffin cells.

机译：牛肾上腺嗜铬细胞中Pb2 +对Ca2 +电流的细胞外抑制和细胞内增强。

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1. Effects of highly neurotoxic, inorganic lead ions (Pb2+) on voltage-dependent calcium channels were investigated with the use of the whole cell patch-clamp technique in bovine adrenal chromaffin cells maintained in short-term primary culture (1-5 days). 2. Extracellularly applied Pb2+ induced a concentration-dependent, reversible inhibition of Ca2+ currents, with an estimated IC50 approximately equal to 3.0 x 10(-7) M free Pb2+. 3. Elevation of the intracellular free Ca2+ concentration above 10(-8) M dose-dependently reduced the amplitude of the initial Ca2+ current and increased the exponential rate of current rundown. 4. Intracellularly applied Pb2+ prevented the Ca(2+)-dependent reduction of the initial Ca2+ current amplitude and altered the current rundown kinetics from exponential to linear. The effect was dose dependent and saturable, with an estimated EC50 approximately equal to 2.0 x 10(-10) M free Pb2+. 5. These results indicate that in contrast to extracellular blockade, intracellular Pb2+promotes Ca2+ currents by attenuating the Ca(2+)-dependent, steady-state inactivation of calcium channels. This provides a novel mechanism through which Pb2+ may disrupt calcium signaling in chronically lead-exposed cells.
机译：1.使用全细胞膜片钳技术，在短期原代培养（1-5天）中维持的牛肾上腺嗜铬细胞中，研究了高度神经毒性的无机铅离子（Pb2 +）对电压依赖性钙通道的影响。 。 2.细胞外施用的Pb2 +诱导了Ca2 +电流的浓度依赖性可逆抑制，估计IC50约等于3.0 x 10（-7）M游离Pb2 +。 3.细胞内游离Ca2 +浓度高于10（-8）M时，剂量依赖性地降低了初始Ca2 +电流的幅度，并增加了电流减少的指数速率。 4.细胞内施用的Pb2 +阻止了Ca（2+）依赖的初始Ca2 +电流幅度的减小，并将电流下降动力学从指数变化为线性。这种作用是剂量依赖性和可饱和的，估计的EC50大约等于2.0 x 10（-10）M游离Pb2 +。 5.这些结果表明，与细胞外阻滞相反，细胞内Pb2 +通过减弱钙通道的Ca（2+）依赖性稳态失活来促进Ca2 +电流。这提供了一种新颖的机制，通过该机制，Pb2 +可以破坏慢性铅暴露细胞中的钙信号传导。

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