Calcium and voltage dependent inactivation of sodium and calcium currents limits calcium influx in Helisoma neurons.

Calcium and voltage dependent inactivation of sodium and calcium currents limits calcium influx in Helisoma neurons.
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DOI:
10.1002/neu.10155
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发表时间:
2003-02
期刊:
Journal of neurobiology
影响因子:
--
通讯作者:
P. J. Torreano;C. Cohan
P. J. Torreano;C. Cohan
中科院分区:
其他
文献类型:
--
作者:
P. J. Torreano;C. Cohan

文献摘要

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细胞内游离钙浓度([Ca2+]i)的控制是细胞存活所必需的,因为这种第二信使在调节许多细胞内过程中起着无处不在和必不可少的作用。由于在膜去极化过程中,大量钙通过电压门控通道流入神经元,因此神经元中的钙调节尤为强烈。在这项研究中,我们检查了离子电流的变化,离子电流可以在电活动期间限制钙流入神经元。我们发现,电刺激Helisoma B4神经元中的[Ca2+]i随着动作电位峰值电压的下降而先升高到峰值,然后放松到较低的浓度。钠钙驱动神经元的[Ca2+]i和动作电位峰值下降是i (Na)和i (Ca)失活的双重表现。I(Na)和I(Ca)均显示电压依赖性失活。此外,I(Na)和I(Ca)在[Ca2+] I超过200 nM时逐渐失活,在电刺激的B4神经元中,浓度很容易达到。发现钙和电压依赖性I(Na)和I(Ca)失活通过降低可激活的I(Ca)的大小和由于峰值动作电位电压降低而激活的可用I(Ca)的百分比来减少持续电刺激期间的钙内流。基于本文数据的计算表明,在持续电刺激期间发生的电压和钙依赖性I(Na)和I(Ca)失活显著减少了钠和钙驱动神经元中的钙内流,从而限制了[Ca2+] I的增加。
The control of free intracellular calcium concentration ([Ca2+]i) is necessary for cell survival because of the ubiquitous and essential role this second messenger plays in regulating numerous intracellular processes. Calcium regulation in neurons is especially vigorous because of the large calcium influx that occurs through voltage-gated channels during membrane depolarization. In this study we examined changes in ionic currents that can limit calcium influx into neurons during electrical activity. We found that the [Ca2+]i in electrically stimulated Helisoma B4 neurons initially increased to a peak and then relaxed to lower concentrations in tandem with a decline in the action potential peak voltage. The decline in [Ca2+]i and the peak action potential voltage in this sodium and calcium driven neuron was found to be a dual manifestation of I(Na) and I(Ca) inactivation. I(Na) and I(Ca) both displayed voltage dependent inactivation. Additionally, I(Na) and I(Ca) progressively inactivated at [Ca2+]i above 200 nM, concentrations readily attained in electrically stimulated B4 neurons. Calcium and voltage dependent I(Na) and I(Ca) inactivation were found to reduce calcium influx during continuous electrical stimulation by decreasing both the magnitude of I(Ca) that could be activated and the percent of the available I(Ca) that would be activated due to the diminished peak action potential voltage. Calculations based on data herein suggest that the voltage and calcium dependent I(Na) and I(Ca) inactivation that occurs during continuous electrical stimulation dramatically reduces calcium influx in this sodium and calcium driven neuron and thus limits the increase in [Ca2+]i.