Amplitude-dependent spike-broadening and enhanced Ca(2+) signaling in GnRH-secreting neurons.
Amplitude-dependent spike-broadening and enhanced Ca(2+) signaling in GnRH-secreting neurons.
复制标题
GnRH 分泌神经元中振幅依赖性尖峰加宽和增强的 Ca(2) 信号传导。
DOI：
10.1016/s0006-3495(00)76384-3
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发表时间：
2000
影响因子：
3.4
通讯作者：
Stojilkovic,SS
中科院分区：
文献类型：
--
作者：
VanGoor,F;LeBeau,AP;Krsmanovic,LZ;Sherman,A;Catt,KJ;Stojilkovic,SS
在促性腺激素释放激素（GT 1）神经元中，钙动员受体的激活诱导持续的膜去极化，使动作电位（AP）波形从尖锐的高振幅转变为宽的低振幅尖峰。在这里，我们的特点是这种转变的发射模式和其对Ca 2+流入实验使用预先记录的尖锐和广泛的AP作为电压钳命令脉冲的影响。作为实验数据的定量测试，还使用了基于GT 1神经元的膜和离子电流特性的数学模型。实验和建模的结果表明，河豚毒素敏感的Na+通道的持续去极化的失活占穗upstroke的幅度减少。随之而来的四乙铵敏感性K+电流激活的减少减缓了膜复极，导致AP增宽。这种放电模式的变化增加了总的L-型Ca 2+电流，并促进AP驱动的Ca 2+内流。GT 1细胞中表达的L型Ca 2+通道的电流-电压关系的漂移允许去极化诱导的AP增宽以促进Ca 2+进入，尽管尖峰幅度降低。因此，GT 1神经元中表达的L型Ca 2+通道的门控特性适合于促进AP驱动的受体和非受体去极化细胞中的Ca 2+内流。
In GnRH-secreting (GT1) neurons, activation of Ca2+-mobilizing receptors induces a sustained membrane depolarization that shifts the profile of the action potential (AP) waveform from sharp, high-amplitude to broad, low-amplitude spikes. Here we characterize this shift in the firing pattern and its impact on Ca2+influx experimentally by using prerecorded sharp and broad APs as the voltage-clamp command pulse. As a quantitative test of the experimental data, a mathematical model based on the membrane and ionic current properties of GT1 neurons was also used. Both experimental and modeling results indicated that inactivation of the tetrodotoxin-sensitive Na+channels by sustained depolarization accounted for a reduction in the amplitude of the spike upstroke. The ensuing decrease in tetraethylammonium-sensitive K+current activation slowed membrane repolarization, leading to AP broadening. This change in firing pattern increased the total L-type Ca2+current and facilitated AP-driven Ca2+entry. The leftward shift in the current-voltage relation of the L-type Ca2+channels expressed in GT1 cells allowed the depolarization-induced AP broadening to facilitate Ca2+entry despite a decrease in spike amplitude. Thus the gating properties of the L-type Ca2+channels expressed in GT1 neurons are suitable for promoting AP-driven Ca2+influx in receptor- and non-receptor-depolarized cells.