Essential role of the persistent sodium current in spike initiation during slowly rising inputs in mouse spinal neurones
Essential role of the persistent sodium current in spike initiation during slowly rising inputs in mouse spinal neurones
复制标题
DOI：
10.1113/jphysiol.2006.107094
复制
发表时间：
2006-08-01
影响因子：
5.5
通讯作者：
Heckman, C. J.
中科院分区：
文献类型：
--
作者：
Kuo, J. J.;Lee, R. H.;Heckman, C. J.
与许多神经元一样，脊髓运动神经元对持续输入做出重复的尖峰反应。然而，每个尖峰后的后超极化 (AHP) 在运动神经元中衰减相对较慢。在此衰减过程中缓慢的去极化应该允许钠 (Na+) 通道失活跟上其激活，从而防止下一个尖峰的启动。我们假设总 Na+ 电流的持续分量提供了产生足够快的上升速率以产生尖峰的机制。在大型培养的脊髓神经元（推测主要是运动神经元）中，低浓度药物利鲁唑对持续钠电流（Na-P）的抑制导致重复放电的丧失。然而，细胞仍然完全有能力对瞬时输入产生尖峰。利鲁唑的这些作用并非由于去极化不足、AHP 增强或持续 Na+ 通道失活所致。为了进一步检验这一假设，使用动力学 Na+ 通道模型进行计算机模拟，该模型比利鲁唑给药提供的 Na-P 相对于瞬态 Na+ 电流 (Na-T) 提供了更大的独立控制。该模型经过调整可产生大量的 Na-P，并对缓慢上升的输入表现出良好的重复发射能力。当 Na-P 急剧减少而不显着改变 Na-T 时，该模型再现了利鲁唑给药的效果，导致重复放电失败，但允许单次尖峰响应急剧瞬变。这些结果有力地支持了 Na-P 在尖峰启动以减缓脊髓神经元输入中的重要作用。 Na-P 可能在决定神经元如何响应持续输入方面发挥重要作用。
Spinal motoneurons, like many neurons, respond with repetitive spiking to sustained inputs. The afterhyperpolarization (AHP) that follows each spike, however, decays relatively slowly in motoneurons. The slow depolarization during this decay should allow sodium (Na+) channel inactivation to keep up with its activation and thus should prevent initiation of the next spike. We hypothesized that the persistent component of the total Na+ current provides the mechanism that generates a rate of rise sufficiently rapid to generate a spike. In large cultured spinal neurons, presumed to be primarily motoneurons, inhibition of persistent sodium current (Na-P) by the drug riluzole at low concentrations resulted in a loss of repetitive firing. However, cells remained fully capable of producing spikes to transient inputs. These effects of riluzole were not due to insufficient depolarization, enhancement of the AHP, or sustained Na+ channel inactivation. To further test this hypothesis, computer simulations were performed with a kinetic Na+ channel model that provided greater independent control of Na-P relative to transient Na+ current (Na-T) than that provided by riluzole administration. The model was tuned to generate substantial Na-P and exhibited good repetitive firing to slowly rising inputs. When Na-P was sharply reduced without significantly altering Na-T, the model reproduced the effects of riluzole administration, inducing failure of repetitive firing but allowing single spikes in response to sharp transients. These results strongly support the essential role of Na-P in spike initiation to slow inputs in spinal neurons. Na-P may play a fundamental role in determining how a neuron responds to sustained inputs.