鸟类脑桥大细胞核频率发放模式的离子通道机制:一个计算模型。
Ion channel mechanisms underlying frequency-firing patterns of the avian nucleus magnocellularis: A computational model.
机构信息
a Roxelyn and Richard Pepper Department of Communication Sciences and Disorders , Northwestern University , Evanston , IL , USA.
b Department of Neurobiology , Northwestern University , Evanston , IL , USA.
出版信息
Channels (Austin). 2017 Sep 3;11(5):444-458. doi: 10.1080/19336950.2017.1327493. Epub 2017 May 8.
We have previously shown that late-developing avian nucleus magnocellularis (NM) neurons (embryonic [E] days 19-21) fire action potentials (APs) that resembles a band-pass filter in response to sinusoidal current injections of varying frequencies. NM neurons located in the mid- to high-frequency regions of the nucleus fire preferentially at 75 Hz, but only fire a single onset AP to frequency inputs greater than 200 Hz. Surprisingly, NM neurons do not fire APs to sinusoidal inputs less than 20 Hz regardless of the strength of the current injection. In the present study we evaluated intrinsic mechanisms that prevent AP generation to low frequency inputs. We constructed a computational model to simulate the frequency-firing patterns of NM neurons based on experimental data at both room and near physiologic temperatures. The results from our model confirm that the interaction among low- and high-voltage activated potassium channels (K and K, respectively) and voltage dependent sodium channels (Na) give rise to the frequency-firing patterns observed in vitro. In particular, we evaluated the regulatory role of K during low frequency sinusoidal stimulation. The model shows that, in response to low frequency stimuli, activation of large K current counterbalances the slow-depolarizing current injection, likely permitting Na closed-state inactivation and preventing the generation of APs. When the K current density was reduced, the model neuron fired multiple APs per sinusoidal cycle, indicating that K channels regulate low frequency AP firing of NM neurons. This intrinsic property of NM neurons may assist in optimizing response to different rates of synaptic inputs.
我们之前已经表明,发育较晚的鸟类细胞核巨细胞(NM)神经元(胚胎[E]天 19-21)在响应变化频率的正弦电流注入时会产生类似于带通滤波器的动作电位(AP)。位于核的中高频区的 NM 神经元优先在 75 Hz 处发射,但仅对大于 200 Hz 的频率输入发射单个起始 AP。令人惊讶的是,NM 神经元不会对小于 20 Hz 的正弦输入发射 AP,无论电流注入的强度如何。在本研究中,我们评估了防止低频输入产生 AP 的内在机制。我们构建了一个计算模型,根据在室温及接近生理温度下的实验数据来模拟 NM 神经元的频率发射模式。我们模型的结果证实,低电压和高电压激活钾通道(K 和 K,分别)和电压依赖性钠通道(Na)之间的相互作用导致了体外观察到的频率发射模式。特别是,我们评估了 K 在低频正弦刺激期间的调节作用。该模型表明,对低频刺激的响应,大 K 电流的激活会抵消缓慢去极化电流的注入,可能允许 Na 关闭状态失活,并防止 AP 的产生。当 K 电流密度降低时,模型神经元在每个正弦周期内发射多个 AP,表明 K 通道调节 NM 神经元的低频 AP 发射。NM 神经元的这种内在特性可能有助于优化对不同突触输入速率的反应。