The Vollum Institute, Oregon Health and Science University, Portland, Oregon 97239, USA.
J Neurosci. 2010 Nov 17;30(46):15479-90. doi: 10.1523/JNEUROSCI.3982-10.2010.
Axonal and nerve terminal action potentials often display a depolarizing after potential (DAP). However, the underlying mechanism that generates the DAP, and its impact on firing patterns, are poorly understood at axon terminals. Here, we find that at calyx of Held nerve terminals in the rat auditory brainstem the DAP is blocked by low doses of externally applied TTX or by the internal dialysis of low doses of lidocaine analog QX-314. The DAP is thus generated by a voltage-dependent Na(+) conductance present after the action potential spike. Voltage-clamp recordings from the calyx terminal revealed the expression of a resurgent Na(+) current (I(NaR)), the amplitude of which increased during early postnatal development. The calyx of Held also expresses a persistent Na(+) current (I(NaP)), but measurements of calyx I(NaP) together with computer modeling indicate that the fast deactivation time constant of I(NaP) minimizes its contribution to the DAP. I(NaP) is thus neither sufficient nor necessary to generate the calyx DAP, whereas I(NaR) by itself can generate a prominent DAP. Dialysis of a small peptide fragment of the auxiliary β4 Na(+) channel subunit into immature calyces (postnatal day 5-6) induced an increase in I(NaR) and a larger DAP amplitude, and enhanced the spike-firing precision and reliability of the calyx terminal. Our results thus suggest that an increase of I(NaR) during postnatal synaptic maturation is a critical feature that promotes precise and resilient high-frequency firing.
轴突和神经末梢动作电位常表现出去极化后电位（DAP）。然而，在轴突末梢，产生 DAP 的潜在机制及其对放电模式的影响知之甚少。在这里，我们发现在大鼠听觉脑干的 Held 神经末梢的壶腹处，DAP 被外部应用低剂量 TTX 或内部透析低剂量 lidocaine 类似物 QX-314 阻断。因此，DAP 是由动作电位尖峰后存在的电压依赖性 Na+电导产生的。从壶腹末端进行电压钳记录显示出复发性 Na+电流（I(NaR)）的表达，其幅度在出生后早期发育过程中增加。Held 壶腹还表达持续的 Na+电流（I(NaP)），但对壶腹 I(NaP)的测量以及计算机建模表明，I(NaP)的快速失活时间常数使其对 DAP 的贡献最小。因此，I(NaP)既不足以也不需要产生壶腹 DAP，而 I(NaR)本身可以产生明显的 DAP。将辅助β4 Na+通道亚基的小肽片段注入未成熟的壶腹（出生后 5-6 天）可增加 I(NaR)和更大的 DAP 幅度，并增强壶腹末端的尖峰发射精度和可靠性。我们的研究结果表明，在出生后突触成熟过程中 I(NaR)的增加是促进精确和有弹性的高频发射的关键特征。
