Calcium channel dynamics limit synaptic release in response to prosthetic stimulation with sinusoidal waveforms.
Calcium channel dynamics limit synaptic release in response to prosthetic stimulation with sinusoidal waveforms.
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DOI：
10.1088/1741-2560/8/4/046005
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发表时间：
2011-08
影响因子：
4
通讯作者：
Fried SI
中科院分区：
文献类型：
--
作者：
Freeman DK;Jeng JS;Kelly SK;Hartveit E;Fried SI
正弦波形的细胞外电刺激已被证明可以通过改变刺激频率优先激活个别类型的视网膜神经元。作为改进优先激活方法的一步，了解这种频率依赖性背后的机制非常重要。为了阐明这些机制，我们实现了视网膜双极细胞的形态学真实模型，并用正弦波形测量了对细胞外刺激的反应。我们将被动膜模型的频率响应与介导突触释放的电压门控钙通道的动力学进行了比较。膜的无源电特性表现出具有相对较高截止频率（标称值= 717 Hz）的低通滤波。该截止频率取决于轴突内阻力，较短和较宽的轴突产生较高的截止频率。然而，我们发现双极细胞突触释放的截止频率主要受到 Land T 型钙通道相对缓慢的开放动力学的限制。钙电流的截止频率非线性地取决于刺激幅度，但对于大范围的膜电位波动仍然低于被动膜模型的截止频率。这些结果表明，虽然有可能在很宽的刺激频率范围内调节双极细胞的膜电位，但突触释放只会在该范围的下限处启动。
Extracellular electric stimulation with sinusoidal waveforms has been shown to allow preferential activation of individual types of retinal neurons by varying stimulus frequency. It is important to understand the mechanisms underlying this frequency dependence as a step towards improving methods of preferential activation. In order to elucidate these mechanisms, we implemented a morphologically realistic model of a retinal bipolar cell and measured the response to extracellular stimulation with sinusoidal waveforms. We compared the frequency response of a passive membrane model to the kinetics of voltage-gated calcium channels that mediate synaptic release. The passive electrical properties of the membrane exhibited lowpass filtering with a relatively high cutoff frequency (nominal value = 717 Hz). This cutoff frequency was dependent on intra-axonal resistance, with shorter and wider axons yielding higher cutoff frequencies. However, we found that the cutoff frequency of bipolar cell synaptic release was primarily limited by the relatively slow opening kinetics of Land T-type calcium channels. The cutoff frequency of calcium currents depended nonlinearly on stimulus amplitude, but remained lower than the cutoff frequency of the passive membrane model for a large range of membrane potential fluctuations. These results suggest that while it may be possible to modulate the membrane potential of bipolar cells over a wide range of stimulus frequencies, synaptic release will only be initiated at the lower end of this range.
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影响因子：
4.4
作者：
de Balthasar, Chloe;Patel, Sweta;Fine, Ione
通讯作者：
Fine, Ione
影响因子：
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Hartveit, E
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作者：
Fohlmeister, JF;Miller, RF
通讯作者：
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