Li X, Bennett D J
University of Alberta, Edmonton, AB T6G 2S2, Canada.
J Neurophysiol. 2007 May;97(5):3314-30. doi: 10.1152/jn.01068.2006. Epub 2007 Mar 14.
Low voltage-activated persistent inward calcium currents (Ca PICs) occur in rat motoneurons and are mediated by Cav1.3 L-type calcium channels (L-Ca current). The objectives of this paper were to determine whether this L-Ca current activates a sustained calcium-activated potassium current (SK current) and examine how such SK currents change with spinal injury. For comparison, the SK current that produces the postspike afterhyperpolarization (mAHP) was also quantified. Intracellular recordings were made from motoneurons of adult acute and chronic spinal rats while the whole sacrocaudal spinal cord was maintained in vitro. Spikes/AHPs were evoked with current injection or ventral root stimulation. Application of the SK channel blocker apamin completely eliminated the mAHP, which was not significantly different in chronic and acute spinal rats. The Ca PICs were measured with slow voltage ramps (or steps) with TTX to block sodium currents. In chronic spinal rats, the PICs were activated at -58.6 +/- 6.0 mV and were 2.2 +/- 1.2 nA in amplitude, significantly larger than in acute spinal rats. Apamin significantly increased the PIC, indicating that there was an SK current activated by L-Ca currents (SK(L) current), which ultimately reduced the net PIC. This SK(L) current was not different in acute and chronic spinal rats. The SK(AHP) and the SK(L) currents were activated by different calcium currents because the mAHP/SK(AHP) was blocked by the N, P-type calcium channel blocker omega-conotoxin MVIIC and was resistant to the L-type calcium channel blocker nimodipine, whereas the L-Ca and SK(L) currents were blocked by nimodipine. Furthermore, the SK(AHP) current activated within 10 ms of the spike, whereas the SK(L) current was delayed approximately 100 ms after the onset of the L-Ca current, suggesting that the SK(L) currents were not as spatially close to the L-Ca currents. Finally, the SK(L) and the L-Ca currents were poorly space clamped, with oscillations at their onset and hysteresis in their activation and deactivation voltages, consistent with currents of dendritic origin. The impact of these dendritic currents was especially pronounced in 15% of motoneurons, where apamin led to uncontrollable L-Ca currents that could not be deactivated, even with large hyperpolarizations of the soma. Thus, although the SK(L) currents are fairly small, they play a critical role in terminating the dendritic L-Ca currents.
低电压激活的持续性内向钙电流（Ca PICs）存在于大鼠运动神经元中，由Cav1.3 L型钙通道介导（L-Ca电流）。本文的目的是确定这种L-Ca电流是否激活持续性钙激活钾电流（SK电流），并研究此类SK电流如何随脊髓损伤而变化。为作比较，还对产生峰后超极化（mAHP）的SK电流进行了量化。在体外维持整个骶尾脊髓的情况下，对成年急性和慢性脊髓大鼠的运动神经元进行细胞内记录。通过电流注入或腹根刺激诱发动作电位/超极化后电位。应用SK通道阻滞剂蜂毒明肽可完全消除mAHP，急性和慢性脊髓大鼠的mAHP无显著差异。用慢电压斜坡（或阶跃）并使用TTX阻断钠电流来测量Ca PICs。在慢性脊髓大鼠中，PICs在-58.6±6.0 mV时被激活，幅度为2.2±1.2 nA，显著大于急性脊髓大鼠。蜂毒明肽显著增加了PIC，表明存在由L-Ca电流激活的SK电流（SK(L)电流），这最终降低了净PIC。这种SK(L)电流在急性和慢性脊髓大鼠中无差异。SK(AHP)和SK(L)电流由不同的钙电流激活，因为mAHP/SK(AHP)被N、P型钙通道阻滞剂ω-芋螺毒素MVIIC阻断，且对L型钙通道阻滞剂尼莫地平有抗性，而L-Ca和SK(L)电流被尼莫地平阻断。此外，SK(AHP)电流在动作电位后10 ms内激活，而SK(L)电流在L-Ca电流开始后约100 ms延迟激活，这表明SK(L)电流在空间上与L-Ca电流不那么接近。最后，SK(L)和L-Ca电流的空间钳制效果较差，在其起始处有振荡，激活和失活电压存在滞后现象，这与树突起源的电流一致。这些树突电流的影响在15%的运动神经元中尤为明显，在这些神经元中，蜂毒明肽会导致无法控制的L-Ca电流，即使对胞体进行大幅度超极化也无法使其失活。因此尽管SK(L)电流相当小，但它们在终止树突L-Ca电流中起关键作用。
