Mechanisms underlying the early phase of spike frequency adaptation in mouse spinal motoneurones
Mechanisms underlying the early phase of spike frequency adaptation in mouse spinal motoneurones
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DOI：
10.1113/jphysiol.2005.086033
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发表时间：
2005-07-15
影响因子：
5.5
通讯作者：
Brownstone, RM
中科院分区：
文献类型：
--
作者：
Miles, GB;Dai, Y;Brownstone, RM
锋电位频率适应（spike frequency adaptation，SFA）是运动神经元重复放电的基本特征。早期SFA（发生在几百毫秒以上）被认为在肌肉收缩的启动中很重要。迄今为止，脊髓MN中SFA的潜在机制仍不清楚。在本研究中，我们使用了全细胞膜片钳记录的MN在腰椎脊髓片制备的运动功能成熟的小鼠和计算机建模的脊髓MN调查SFA的机制。在电流钳模式下全细胞记录期间应用的药理学阻断剂表明，中等的AHP电导（apamin）、BK型Ca 2+依赖性K+通道（iberiotoxin）、电压激活的Ca 2+通道（CdCl2）、M电流（利诺吡啶）和持续性Na+电流（利鲁唑）对于SFA来说都是不必要的。Na+通道的可用性，包括动作电位振幅，动作电位阈值和动作电位的最大去极化率的测量被发现与瞬时放电频率相关，这表明快速，失活Na+通道的可用性参与SFA。在电压钳模式中的Na+电导的表征表明，它经历了缓慢的失活与SFA的时间过程相似。当实验测量参数的快速，失活Na+电导（包括慢失活）纳入MN模型，SFA可以忠实地再现。从该模型中去除缓慢灭活足以去除SFA。这些数据表明，缓慢失活的快速，失活Na+电导可能是脊髓MN早期SFA的关键机制。
Spike frequency adaptation (SFA) is a fundamental property of repetitive firing in motoneurones (MNs). Early SFA (occurring over several hundred milliseconds) is thought to be important in the initiation of muscular contraction. To date the mechanisms underlying SFA in spinal MNs remain unclear. In the present study, we used both whole-cell patch-clamp recordings of MNs in lumbar spinal cord slices prepared from motor functionally mature mice and computer modelling of spinal MNs to investigate the mechanisms underlying SFA. Pharmacological blocking agents applied during whole-cell recordings in current-clamp mode demonstrated that the medium AHP conductance (apamin), BK-type Ca2+-dependent K+ channels (iberiotoxin), voltage-activated Ca2+ channels (CdCl2), M-current (linopirdine) and persistent Na+ currents (riluzole) are all unnecessary for SFA. Measurements of Na+ channel availability including action potential amplitude, action potential threshold and maximum depolarization rate of the action potential were found to correlate with instantaneous firing frequency suggesting that the availability of fast, inactivating Na+ channels is involved in SFA. Characterization of this Na+ conductance in voltage-clamp mode demonstrated that it undergoes slow inactivation with a time course similar to that of SFA. When experimentally measured parameters for the fast, inactivating Na+ conductance (including slow inactivation) were incorporated into a MN model, SFA could be faithfully reproduced. The removal of slow inactivation from this model was sufficient to remove SFA. These data indicate that slow inactivation of the fast, inactivating Na+ conductance is likely to be the key mechanism underlying early SFA in spinal MNs.