Haghdoost-Yazdi Hashem, Janahmadi Mahyar, Behzadi Gila
Department of Physiology and Medical Physics, Faculty of Medicine, Qazvin University of Medical Sciences, Qazvin, Iran.
Brain Res. 2008 May 30;1212:1-8. doi: 10.1016/j.brainres.2008.03.030. Epub 2008 Mar 27.
Cerebellar Purkinje cells (PCs) are the sole output neurons of the cerebellar cortex. Mature PCs discharge either tonically Na+ spikes or bursts of Na+ spikes ending to a Ca2+ spike. These cells express inactivating and non-inactivating large conductance Ca2+ -dependent K+ (BK) channels in their soma and dendrites. Somatic intracellular recording of acutely prepared brain slices was performed to examine the role of BK channels-mediated current in the tonic and burst firing of PCs. Continuous injection of a negative DC current was used to both suppress the spontaneous activity and stabilize the resting membrane potential around -70 mV. Then, the short depolarizing current injection was used to evoke spike discharge. For establishing of the burst firing, 4-aminopyridine (4-AP) was bath applied to the bath solution. Blockade of BK channels with iberiotoxin (IbTx); a specific blocker of BK channels, did not affect the Na+ spike configuration in the tonic firing but caused a remarkable change in the shape of Na+ and Ca2+ spikes in 4-AP-induced burst. Our results showed that during the burst firing, strong activation of IbTx-sensitive BK channels enhances the amplitude of fast afterhyperpolarization while decreases the duration of both Na+ and Ca2+ spikes. The current from these channels contributes to both the repolarizing of Na+ spike in the burst and setting of the amplitude of post-pulse AHP that occurs immediately after a depolarizing pulse. These data reveal an important role of IbTx-sensitive BK current in regulating of the spike configuration during the burst firing of PCs.
小脑浦肯野细胞（PCs）是小脑皮质的唯一输出神经元。成熟的PCs要么持续发放Na⁺尖峰，要么发放以Ca²⁺尖峰结束的Na⁺尖峰簇。这些细胞在其胞体和树突中表达失活和非失活的大电导Ca²⁺依赖性K⁺（BK）通道。对急性制备的脑片进行体细胞内记录，以研究BK通道介导的电流在PCs的持续发放和簇发放中的作用。持续注入负向直流电流以抑制自发活动并将静息膜电位稳定在-70 mV左右。然后，使用短时间的去极化电流注入来诱发尖峰放电。为了建立簇发放，将4-氨基吡啶（4-AP）加入浴液中。用iberiotoxin（IbTx）阻断BK通道；BK通道的特异性阻断剂，不影响持续发放中的Na⁺尖峰形态，但在由4-AP诱导的簇发放中引起Na⁺和Ca²⁺尖峰形状的显著变化。我们的结果表明，在簇发放期间，IbTx敏感的BK通道的强烈激活增强了快速超极化后的幅度，同时缩短了Na⁺和Ca²⁺尖峰的持续时间。这些通道的电流有助于簇发放中Na⁺尖峰的复极化以及去极化脉冲后立即出现的脉冲后超极化（AHP）幅度的设定。这些数据揭示了IbTx敏感的BK电流在调节PCs簇发放期间的尖峰形态中的重要作用。
