Schmid S, Guenther E
Department of Pathophysiology of Vision and Neuro-Ophthalmology, University Eye Hospital, Tübingen, Germany.
Neuroscience. 1998 Jul;85(1):249-58. doi: 10.1016/s0306-4522(97)00644-1.
Changes in the kinetic properties of voltage-activated sodium currents (I(Na)) were studied in rat retinal ganglion cells during in vivo differentiation. Whole-cell recordings from cells maintained as retinal slices or whole-mounts were examined using the patch-clamp technique in the perforated patch mode. Voltage-clamp recordings revealed significant ontogenetic modifications in key properties of I(Na) and the present study described for the first time the detailed time course of such alterations. I(Na) was first expressed on embryonic day 17/18 (E17/18). Current density increased during development from an average of -81 pA/pF on E17/18 to a maximum of -747pA/pF on postnatal day 10/12 (P10/12). Simultaneously, the activation of I(Na) shifted towards more negative potentials, reflected by a shift in the potential of half-activation from -14.1 mV on E17/18 to - 37.5 mV on P10/12. No significant changes in these parameters were observed after P10/12. Steady-state inactivation shifted first towards more positive potentials, reflected by a shift in the potential of half-inactivation from -51 mV on E17/18 to -38 mV on P3/5, but shifted back towards more negative values thereafter (-44 mV in the adult). The most striking feature of I(Na) in rat RGCs was a transient slowing of I(Na) kinetics that was never described before. Time to peak and decay time constants increased between E20 and P5, resulting in slow and broad sodium currents within a developmental period that is characterized by intensive synaptogenesis in the target structures of retinal ganglion cells and maximum retinal ganglion cell death. Thereafter, time to peak and decay time constants decreased again to values found before E20, resulting in rapid sodium spikes. In conclusion, sodium currents in rat retinal ganglion cells displayed substantial electrophysiological changes during pre- and postnatal development. These changes in the sodium system had different temporal time patterns, indicating that they may play specific roles during the development of the visual system.
在体内分化过程中，研究了大鼠视网膜神经节细胞中电压门控钠电流（I(Na)）动力学特性的变化。使用穿孔膜片钳技术对维持为视网膜切片或整装片的细胞进行全细胞记录。电压钳记录显示I(Na)的关键特性存在显著的个体发育变化，本研究首次描述了此类变化的详细时间进程。I(Na)在胚胎第17/18天（E17/18）首次表达。在发育过程中，电流密度从E17/18时的平均-81 pA/pF增加到出生后第10/12天（P10/12）的最大值-747 pA/pF。同时，I(Na)的激活向更负的电位移动，这通过半激活电位从E17/18时的-14.1 mV移至P10/12时的-37.5 mV得以体现。在P10/12之后，这些参数未观察到显著变化。稳态失活首先向更正的电位移动，这通过半失活电位从E17/18时的-51 mV移至P3/5时的-38 mV得以体现，但此后又移回更负的值（成年时为-44 mV）。大鼠视网膜神经节细胞中I(Na)最显著的特征是I(Na)动力学的短暂减慢，这在此前从未被描述过。从E20到P5，峰值时间和衰减时间常数增加，导致在一个以视网膜神经节细胞靶结构中密集的突触形成为特征且视网膜神经节细胞死亡最多的发育时期内，钠电流缓慢且宽阔。此后，峰值时间和衰减时间常数再次下降至E20之前的值，导致快速的钠峰。总之，大鼠视网膜神经节细胞中的钠电流在出生前和出生后发育过程中表现出显著的电生理变化。钠系统的这些变化具有不同的时间模式，表明它们可能在视觉系统发育过程中发挥特定作用。
