Li Yunru, Bennett David J
Centre for Neuroscience, University of Alberta, Edmonton, Canada.
J Neurophysiol. 2003 Aug;90(2):857-69. doi: 10.1152/jn.00236.2003. Epub 2003 Apr 30.
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 S2 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 microM nimodipine or 400 microM Cd2+. The PIC that remained during a calcium channel blockade (in Cd2+) was completely and rapidly blocked by tetrodotoxin (TTX; 0.5 to 2 microM), 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.
慢性脊髓损伤后，运动神经元会表现出大的平台电位（由短暂输入触发的持续去极化），这在肌肉痉挛和痉挛状态的发展中起主要作用（Bennett等人，2001a，b）。本研究检测了这些平台电位背后的电压门控持续性内向电流（PICs）。成年大鼠在S2骶髓水平进行脊髓横断，2个月后，当痉挛状态出现时，对损伤平面以下的运动神经元进行细胞内记录。为了进行记录，将整个骶尾脊髓取出，置于正常人工脑脊液（nACSF）中进行体外培养，不施加神经调质。在缓慢的三角电压钳指令（斜坡）期间，一个PIC被激活，阈值为-54.2±4.8 mV（类似于平台电位阈值），峰值电流为2.88±0.95 nA，并在电压-电流关系中产生一个明显的负斜率区域。这种PIC部分由Cav1.3 L型钙通道介导，因为它阈值较低，并且可被10至20 μM尼莫地平或400 μM Cd2+显著降低。在钙通道阻断（在Cd2+中）期间仍存在的PIC被河豚毒素（TTX；0.5至2 μM）完全且迅速地阻断，因此是一种对TTX敏感的持续性钠电流。这种持续性钠电流在低于动作电位阈值约7 mV时迅速激活（动作电位阈值为-46.1±4.5 mV），约占总PIC初始峰值的1/2，部分失活后仅占持续性PIC的约1/3（在5至10秒时），并且随着超极化迅速失活（<50毫秒）。当首先将TTX加入浴槽时，可以单独观察到对尼莫地平敏感的持续性钙电流（L型）；它激活缓慢（>250毫秒），阈值较低但可变（略高于或低于动作电位阈值），占总PIC初始峰值的约另一半（在加入TTX之前），通常不会随时间失活（占持续性PIC的约三分之二），并且随着超极化缓慢失活至静息状态（>300毫秒）。总之，慢性脊髓损伤大鼠的运动神经元中会自发产生低阈值的持续性钙电流（Cav1.3）和钠电流，这些电流能够形成大的、快速激活的平台电位，最终导致痉挛状态。
