The hyperpolarization-activated current (I-h) and its contribution to pacemaker activity in rat CA1 hippocampal stratum oriens-alveus interneurones
The hyperpolarization-activated current (I-h) and its contribution to pacemaker activity in rat CA1 hippocampal stratum oriens-alveus interneurones
复制标题
DOI：
10.1113/jphysiol.1996.sp021754
复制
发表时间：
1996-11-15
影响因子：
5.5
通讯作者：
McBain, CJ
中科院分区：
文献类型：
--
作者：
Maccaferri, G;McBain, CJ
1.采用全细胞膜片钳技术和穿孔膜片钳技术研究了大鼠海马层向-肺泡间神经元的超极化激活电流（I-h）及其在起搏活动中的作用.电压钳记录显示I-h是一种缓慢激活的内向电流，通过超极化步骤激活（保持电位，V-h = -40 mV），逆转电位接近-30 mV。其激活曲线范围为-50至-120 mV，激活中点为-84.1 mV。外部应用Cs+（2-5 mM）和ZD 7288（100 μ M）可以阻断I-h，但Ba 2+（1 mM）不能阻断I-h。4.去甲肾上腺素和异丙肾上腺素均通过与I-h激活曲线移动一致的机制增强I-h。在电流钳条件下（V-h = -60 mV），ZD 7288诱导膜超极化，同时膜输入电阻增加，消除超极化电流注入产生的电压暂降.对电流-放电关系的分析表明，阻断I-h后，与放电后期相比，放电早期出现的放电频率有差异地增加.当应用于自发放电细胞时，ZD 7288通过选择性地改变峰间期的时间过程来降低放电频率，同时对其他动作电位特征的影响最小。同样地，异丙肾上腺素通过对后超极化和峰间期的作用增加自发放电频率。这些结果为I-h参与海马层-肺泡间神经元的兴奋性和自发放电的产生提供了证据。
1. The hyperpolarization-activated current (I-h) and its role in pacemaking activity in rat hippocampal stratum oriens-alveus interneurones was studied using whole-cell and perforated patch-clamp configurations.2. Voltage-clamp recordings revealed I-h as a slowly activating, inward current, activated by hyperpolarizing steps (holding potential, V-h = -40 mV), with a reversal potential close to -30 mV. Its activation curve ranged from similar to-50 to -120 mV with a mid-activation point of -84.1 mV.3. I-h was blocked by external application of Cs+ (2-5 mM) and ZD7288 (100 mu M), but not by Ba2+(1 mM).4. I-h was potentiated by both noradrenaline and isoprenaline by a mechanism consistent with a shift in the I-h activation curve.5. Under current-clamp conditions (V-h = -60 mV), ZD7288 induced a membrane hyperpolarization concomitant with an increase in the membrane input resistance and abolished the voltage sag generated by hyperpolarizing current injection.6. Analysis of the current-discharge relationship revealed that block of I-h differentially increased the firing frequency of spikes occurring early in the train compared with those occurring late in the discharge.7. When applied to spontaneously firing cells, ZD7288 reduced the firing frequency by selectively altering the time course of the interspike interval, while minimally affecting other action potential characteristics. Similarly, isoprenaline increased the spontaneous firing frequency by an effect exclusively on the after hyperpolarization and interspike interval.8. These results provide evidence for the involvement of I-h in the excitability and generation of spontaneous firing in hippocampal stratum oriens-alveus interneurones.