Stabilization of Ca current in Purkinje neurons during high-frequency firing by a balance of Ca-dependent facilitation and inactivation.
Stabilization of Ca current in Purkinje neurons during high-frequency firing by a balance of Ca-dependent facilitation and inactivation.
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DOI：
10.4161/chan.3.6.9838
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发表时间：
2009-11
期刊：
影响因子：
--
通讯作者：
Raman IM
中科院分区：
文献类型：
--
作者：
Benton MD;Raman IM
浦肯野神经元在小脑介导的行为中以约50次/秒的速度发出自发动作电位，并产生超过100次/秒的动作电位。许多电压门控通道，包括钙通道，可以通过重复刺激失活和/或促进，这提出了一个问题，即这些通道如何对规则的、快速的去极化序列做出反应。为了测试在放电过程中钙电流是否被调制，我们记录了30-33°C(1 MMCa)下急性分离的小鼠浦肯野神经元的电压钳钙电流，该电流主要由P-型钙通道携带。用0.5 mM的细胞内EGTA，1秒的自发动作电位波形或50赫兹的短暂去极化步骤均可诱发稳定的钙尾电流，并保持在整个序列中第一尾电流的5%以内。高频列车(100和200赫兹)最大失活10%。为了测试这种钙电流的稳定性是由于缺乏调制还是由于促进和失活之间的平衡，我们操纵了钙离子(钙对钙)和钙缓冲(0.5对10 mM EGTA)。在缓冲较低的情况下，BA加速了1秒序列诱发的初始失活，但在200赫兹时使失活幅度减小，这与高频时的早期钙依赖易化(CDF)和晚期钙依赖失活(CDI)一致。增加钙缓冲液有利于CDF。这些数据表明，稳定的钙电流幅度是CDF、CDI和电压依赖性失活平衡的结果。这种适度的净钙依赖调节可能有助于浦肯野神经元维持长时间规则放电和突触传递的能力。
Purkinje neurons fire spontaneous action potentials at ~50 spikes/sec and generate more than 100 spikes/sec during cerebellum-mediated behaviors. Many voltage-gated channels, including Ca channels, can inactivate and/or facilitate with repeated stimulation, raising the question of how these channels respond to regular, rapid trains of depolarizations. To test whether Ca currents are modulated during firing, we recorded voltage-clamped Ca currents, predominantly carried by P-type Ca channels, from acutely dissociated mouse Purkinje neurons at 30–33°C (1 mM Ca). With 0.5 mM intracellular EGTA, 1-second trains of either spontaneous action potential waveforms or brief depolarizing steps at 50 Hz evoked Ca tail currents that were stable, remaining within 5% of the first tail current throughout the train. Higher frequency trains (100 and 200 Hz) elicited a maximal inactivation of <10%. To test whether this stability of Ca currents resulted from a lack of modulation or from an equilibrium between facilitation and inactivation, we manipulated the permeant ion (Ca vs. Ba) and Ca buffering (0.5 vs. 10 mM EGTA). With low buffering, Ba accelerated the initial inactivation evoked by 1-second trains, but reduced its extent at 200 hz, consistent with an early calcium-dependent facilitation (CDF) and late calcium-dependent inactivation (CDI) at high frequencies. Increasing the Ca buffer favored CDF. These data suggest that stable Ca current amplitudes result from a balance of CDF, CDI, and voltage-dependent inactivation. This modest net Ca-dependent modulation may contribute to the ability of Purkinje neurons to sustain long periods of regular firing and synaptic transmission.
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DOI：
10.1073/pnas.2237000100
发表时间：
2003-12-23
影响因子：
11.1
作者：
Lee, A;Zhou, H;Catterall, WA
通讯作者：
Catterall, WA
影响因子：
16.2
作者：
Mochida, Sumiko;Few, Alexandra P.;Catterall, William A.
通讯作者：
Catterall, William A.
影响因子：
5.3
作者：
Chaudhuri, D;Chang, SY;Yue, DT
通讯作者：
Yue, DT
影响因子：
5.5
作者：
Edgerton, JR;Reinhart, PH
通讯作者：
Reinhart, PH
影响因子：
2.5
作者：
Levin, Stephen I.;Khaliq, Zayd M.;Meisler, Miriam H.
通讯作者：
Meisler, Miriam H.