Slow potentiation of CaィイD12+ィエD1-dependent depolarizing spike afterdepdarization in pyramidal, cells.

一些锥体细胞的规则尖峰模式已被证明转变为快速有节奏的爆发模式。快速有节奏的爆发神经元被认为在唤起认知或短期记忆排练中观察到的伽马带脑电图振荡中起关键作用。由于去极化后电位（DAP）的增强似乎参与了放电模式的转变，我们采用全细胞记录方法研究了大鼠额叶皮质切片锥体细胞中去极化后电位及其增强的离子机制。发现DAP的产生是由Ca2+依赖的阳离子电流介导的，该阳离子电流可以表示为慢尾电流(I)，在电压箝位条件下，在去极化脉冲偏移后持续几秒钟。用咖啡因（10 mM）浸泡延长慢尾。在咖啡因存在的情况下，重复使用去极化脉冲会产生一个持续几十秒的慢得多的尾波。尾电流和荧光比的同时测量表明，阳离子通道的Ca2+敏感性在[Ca2+]i瞬态增加后上调。CaM KII的抑制剂KN-62和KN-93抑制了慢尾is的增强而不影响CICR，这表明CaM KII的激活可能在Ca2+依赖性阳离子通道的上调中起关键作用。这表明，在咖啡因的存在下，较慢的尾i的产生在很大程度上取决于[Ca2+]i的短暂增加。增加的Ca2+可能反过来激活CaM KII使阳离子通道磷酸化。这与我们之前的观察一致，即反复应用强去极化诱导快速节律性突发放电，这是DAP增强的结果。

Regular spiking pattern in some pyramidal cells has been demonstrated to be changed into fast rhythmic bursting pattern. Fast rhythmic bursting neurons are presumed to play a crucial role in evoking gamma-band EEG oscillation that is observed on cognition or on rehearsal of short term memory. Since the enhancement of depolarizing afterpotentials (DAP) appeared to be involved in the transformation of firing pattern, we investigated the ionic mechanisms underlying the DAP and its potentiation in pyramidal cells in rat frontal cortical slices using the whole-cell recording method. The generation of DAP was found to be mediated by a Ca2+ dependent cationic current which can be expressed as a slow tail current (I),lasting for a few seconds after the offset of depolarization pulses under voltage clamp conditions. Slow tail-Is were prolonged by bath application of caffeine (10 mM). Repetitive application of depolarizing pulses in the presence of caffeine led to a generation of a much slower tail-I lasting for a few tens of seconds. Simultaneous measurements of tail current and fluorescent ratio revealed that the Ca2+ sensitivity of the cationic channel is upregulated after a transient increase in [Ca2+]i. KN-62 and KN-93, inhibitors of CaM KII, suppressed this enhancement of slow tail-Is without affecting CICR, indicating that activation of CaM KII may play a crucial role in the upregulation of Ca2+ dependent cationic channels. It was suggested that the generation of slower tail-I in the presence of caffeine was largely dependent on the transient increase in [Ca2+]i. The increased Ca2+ may in turn activate CaM KII to phosphorylate cationic channels. This would be consistent with our previous observation that repetitive application of strong depolarization induced fast rhythmic burst firing as a consequence of an enhancement of DAP.