Persistent sodium and calcium currents cause plateau potentials in motoneurons of chronic spinal rats
Persistent sodium and calcium currents cause plateau potentials in motoneurons of chronic spinal rats
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DOI：
10.1152/jn.00236.2003
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发表时间：
2003-08-01
影响因子：
2.5
通讯作者：
Bennett, DJ
中科院分区：
文献类型：
--
作者：
Li, YR;Bennett, DJ
慢性脊髓损伤后，运动神经元表现出较大的平台电位（由短暂输入触发的持续去极化），这在肌肉痉挛和痉挛的发展中起主要作用（Bennett等人，2001a,b）。本研究考察了这些高原下的电压门控持续内向电流（PICs）。成年大鼠在S-2骶脊髓水平脊髓化，2个月后，当痉挛发生时，从损伤下方的运动神经元进行细胞内记录。为了记录，切除整个骶尾脊髓，在体外正常人工脑脊液（nACSF）中保存，不使用神经调节剂。在缓慢的三角形电压箝位命令（斜坡）期间，PIC被激活，阈值为-54.2 +/- 4.8 mV（类似于平台阈值），峰值电流为2.88 +/- 0.95 nA，并在V-I关系中产生明显的负斜率区域。这种PIC部分是由Cav1.3 l型钙通道介导的，因为它的阈值较低，尼莫地平10 ~ 20 μ m或Cd2+ 400 μ m显著降低。在钙通道阻断（Cd2+）期间保留的PIC被河豚毒素（TTX； 0.5至2 muM）完全和迅速阻断，因此是TTX敏感的持久钠电流。这种持续的钠电流在低于峰值阈值（峰值阈值-46.1 +/- 4.5 mV）约7 mV时被快速激活，贡献了大约1/2的总PIC初始峰值，部分失活仅贡献了大约1/3的持续PIC（在5到10秒），并在超极化时迅速失活（< 50 ms）。先加入TTX后，分离得到尼莫地平敏感的l型持续钙电流；它缓慢激活（> 250 ms），有一个低但可变的阈值（略高于或低于峰值阈值），贡献了总PIC初始峰值的另外大约1/2（在TTX之前），通常不随时间而失活（贡献了大约三分之二的持续PIC），并且在超极化休息时缓慢失活（> 300 ms）。总之，低阈值持续性钙（Cav1.3）和钠电流在慢性脊髓大鼠的运动神经元中自发形成，这些电流使大的、快速激活的平台最终导致痉挛。
After chronic spinal cord injury motoneurons exhibit large plateau potentials (sustained depolarizations triggered by brief inputs) that play a primary role in the development of muscle spasms and spasticity (Bennett et al. 2001a,b). The present study examined the voltage-gated persistent inward currents (PICs) underlying these plateaus. Adult rats were spinalized at the S-2 sacral spinal level and after 2 mo, when spasticity developed, intracellular recordings were made from motoneurons below the injury. For recording, the whole sacrocaudal spinal cord was removed and maintained in vitro in normal artificial cerebral spinal fluid (nACSF), without application of neuromodulators. During a slow triangular voltage-clamp command (ramp) a PIC was activated with a threshold of -54.2 +/- 4.8 mV (similar to plateau threshold), with a peak current of 2.88 +/- 0.95 nA and produced a pronounced negative-slope region in the V-I relation. This PIC was in part mediated by Cav1.3 L-type calcium channels because it was low threshold and significantly reduced by 10 to 20 muM nimodipine or 400 muM Cd2+. The PIC that remained during a calcium channel blockade (in Cd2+) was completely and rapidly blocked by tetrodotoxin (TTX; 0.5 to 2 muM), and thus was a TTX-sensitive persistent sodium current. This persistent sodium current was activated rapidly about 7 mV below the spike threshold ( spike threshold -46.1 +/- 4.5 mV), contributed approximately 1/2 of the initial peak of the total PIC, inactivated partly to contribute only approximately 1/3 of the sustained PIC (at 5 to 10 s), and deactivated rapidly with hyperpolarization (< 50 ms). When TTX was added to the bath first, the nimodipine-sensitive persistent calcium current (L-type) was seen in isolation; it was slowly activated (> 250 ms), had a low but variable threshold (either slightly above or below the spike threshold), contributed the other approximately 1/2 of the initial peak of the total PIC (before TTX), did not usually inactivate with time (contributed approximately two-thirds of the sustained PIC), and deactivated slowly with hyperpolarization to rest (in > 300 ms). In summary, low-threshold persistent calcium (Cav1.3) and sodium currents spontaneously develop in motoneurons of chronic spinal rats and these enable large, rapidly activated plateaus that ultimately lead to spasticity.