Apamin-sensitive calcium-activated potassium currents (SK) are activated by persistent calcium currents in rat motoneurons

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 (SKL current), which ultimately reduced the net PIC. This SKL current was not different in acute and chronic spinal rats. The SKAHP and the SKL currents were activated by different calcium currents because the mAHP/SKAHP 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 SKL currents were blocked by nimodipine. Furthermore, the SKAHP current activated within 10 ms of the spike, whereas the SKL current was delayed similar to 100 ms after the onset of the L-Ca current, suggesting that the SKL currents were not as spatially close to the L-Ca currents. Finally, the SKL 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 SKL currents are fairly small, they play a critical role in terminating the dendritic L-Ca currents.