Effects of depolarization evoked Na+ influx on intracellular Na+ concentration at neurosecretory nerve endings.

Effects of depolarization evoked Na+ influx on intracellular Na+ concentration at neurosecretory nerve endings.
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去极化引起的 Na 内流对神经分泌神经末梢细胞内 Na 浓度的影响。

DOI:
10.1016/s0306-4522(98)00065-7
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发表时间:
1998
期刊:
影响因子:
3.3
通讯作者:
Stuenkel,EL
Stuenkel,EL
中科院分区:
医学3区
文献类型:
--
作者:
Turner,D;Stuenkel,EL

文献摘要

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应用膜片钳技术,结合光学显微镜下观察的神经垂体末梢细胞内游离Na+浓度的变化,研究了重复刺激引起的Na+内流与[Na+]i变化的关系。应用电压钳下的阶跃去极化诱发河豚毒素敏感的内向电流依赖于细胞外Na+,并表现出快速激活和失活特性。这些特征证实了诱发电流为电压依赖性Na+电流。应用模拟动作电位频率和持续时间的阶跃去极化组成的刺激序列,发现导致[Na+]i增加。[Na+] i的变化与刺激频率和刺激时间有关。[Na+] i的变化在40 Hz频率下最大,在约2.4mM的连续刺激30 s时变化最大。在低Na+负荷刺激的初始阶段,以摩尔量表示的钠内流导致[Na+]几乎成正比地增加。当表示为电荷密度(pC/mm 2)Na+内流被发现增加与较小直径的神经末梢一样,在[Na+] i的变化率在响应于应用重复步骤去极化。重复的步骤去极化,模拟冲动活动,侵入神经内分泌神经末梢在体内响应生理需求的激素分泌导致增加[Na+]i。据推测,这种增加的[Na+] i可能通过改变细胞内钙调节间接地对分泌反应产生调节作用,或者可能通过对分泌机制的直接作用。
Electrophysiological measurements of voltage-dependent Na+influx using patch-clamp methodology were combined with optical monitoring of the free intracellular Na+concentration in isolated rat neurohypophysial nerve endings to determine the relationship between Na+influx generated by repetitive stimulation and change in [Na+]i. Application of step depolarizations under voltage-clamp-evoked tetrodotoxin-sensitive inward currents that were dependent upon extracellular Na+and that exhibited rapid activation and inactivation properties. These characteristics substantiated the evoked current as a voltage-dependent Na+current. Application of stimulus trains consisting of step depolarizations that mimick in frequency and duration those of action potentials were found to result in increases in [Na+]i. The induced change in [Na+]iwas found to be related to the frequency and period of stimulation. Changes in [Na+]iwere greatest at frequencies of 40Hz and gave maximal changes with 30s of continuous stimulation of approximately 2.4mM. Sodium influx expressed as a molar quantity resulted in a nearly directly proportional increase in [Na+]iduring the initial period of stimulation at low Na+loads. When expressed as a charge density (pC/mm2) Na+influx was found to increase with smaller diameter nerve endings as did the rate of change in [Na+]iin response to applied repetitive step depolarizations. Repetitive step depolarizations which simulate impulse activity that invade neuroendocrine nerve endings in vivo in response to physiological demand for hormone secretion resulted in an increased [Na+]i. It is postulated that this increased [Na+]imay provide a modulatory influence on the secretory response indirectly via alteration of intracellular calcium regulation or, perhaps, via a direct action on the secretory mechanism.