Ionic mechanisms of autorhythmic firing in rat cerebellar Golgi cells
Ionic mechanisms of autorhythmic firing in rat cerebellar Golgi cells
复制标题
DOI：
10.1113/jphysiol.2006.110858
复制
发表时间：
2006-08-01
影响因子：
5.5
通讯作者：
D'Angelo, Egidio
中科院分区：
文献类型：
--
作者：
Forti, Lia;Cesana, Elisabetta;D'Angelo, Egidio
高尔基细胞(GOCs)是小脑颗粒层(GL)中抑制性中间神经元的主要类型，虽然被认为在小脑网络功能中起着中心作用，但其兴奋性仍未被研究。GOCs在体内和切片中有节奏地放电，但尚不清楚这种活动是否源于起搏器离子机制。我们通过结合松散细胞附着(LCA)和全细胞(WC)记录，在3周龄大鼠的急性小脑切片中探讨了这一问题。GOCs在1-10赫兹(室温)和2-20赫兹(35-37摄氏度)表现出自发放电，在快速突触受体阻滞剂以及mGluR和GABA(B)受体的存在下持续存在，因此在我们的情况下，表现为起搏神经元。ZD 7288(20微米)是一种有效的超极化激活电流(I-H)阻滞剂，可减慢起搏器频率。亚阈值Na+电流(I-Na，I-SUB)的作用不能直接测试，但我们在亚阈值电压范围内观察到了对TTX敏感的、非失活的Na+电流。在研究复极电流时，我们发现产生神经元M型K+(I-M)电流的KCNQ K+通道激动剂瑞替加宾(5 MU M)降低了阈值区域的GOC兴奋性。KCNQ通道拮抗剂XE991(5 MU M)不改变放电，提示Goc I-M对XE991的敏感性较低。棘波复极后出现后超极化(AHP)，后超极化由阿帕明敏感的钙依赖钾电流(I-APA)支持。阻断I-APA可降低起搏精度，但不改变起搏平均频率。我们认为前馈去极化是由I-h和I-Na、I-SUB维持的，而延迟的复极化反馈涉及I-M类电流，其性质有待于表征。GOC起搏的多种离子机制为精细调节放电频率和精确度提供了物质基础，从而影响GOCs对小脑GL的周期性抑制作用。
Although Golgi cells (GoCs), the main type of inhibitory interneuron in the cerebellar granular layer (GL), are thought to play a central role in cerebellar network function, their excitable properties have remained unexplored. GoCs fire rhythmically in vivo and in slices, but it was unclear whether this activity originated from pacemaker ionic mechanisms. We explored this issue in acute cerebellar slices from 3-week-old rats by combining loose cell-attached (LCA) and whole-cell (WC) recordings. GoCs displayed spontaneous firing at 1-10 Hz (room temperature) and 2-20 Hz (35-37 degrees C), which persisted in the presence of blockers of fast synaptic receptors and mGluR and GABA(B) receptors, thus behaving, in our conditions, as pacemaker neurons. ZD 7288 (20 mu M), a potent hyperpolarization-activated current (I-h) blocker, slowed down pacemaker frequency. The role of subthreshold Na+ currents (I-Na,I-sub) could not be tested directly, but we observed a robust TTX-sensitive, non-inactivating Na+ current in the subthreshold voltage range. When studying repolarizing currents, we found that retigabine (5 mu M), an activator of KCNQ K+ channels generating neuronal M-type K+ (I-M) currents, reduced GoC excitability in the threshold region. The KCNQ channel antagonist XE991 (5 mu M) did not modify firing, suggesting that GoC I-M has low XE991 sensitivity. Spike repolarization was followed by an after-hyperpolarization (AHP) supported by apamin-sensitive Ca2+-dependent K+ currents (I-apa). Block of I-apa decreased pacemaker precision without altering average frequency. We propose that feed-forward depolarization is sustained by I-h and I-Na,I-sub, and that delayed repolarizing feedback involves an I-M-like current whose properties remain to be characterized. The multiple ionic mechanisms shown here to contribute to GoC pacemaking should provide the substrate for fine regulation of firing frequency and precision, thus influencing the cyclic inhibition exerted by GoCs onto the cerebellar GL.