Persistent Sodium Currents and Repetitive Firing in Motoneurons of the Sacrocaudal Spinal Cord of Adult Rats

Abstract

Months after sacral spinal transection in rats (chronic spinal rats), motoneurons below the injury exhibit large, low-threshold persistent inward currents (PICs), composed of persistent sodium currents (Na PICs) and persistent calcium currents (Ca PICs). Here, we studied whether motoneurons of normal adult rats also exhibited Na and Ca PICs when the spinal cord was acutely transected at the sacral level (acute spinal rats) and examined the role of the Na PIC in firing behavior. Intracellular recordings were obtained from motoneurons of acute and chronic spinal rats while the whole sacrocaudal spinal cord was maintained in vitro. Compared with chronic spinal rats, motoneurons of acute spinal rats were more difficult to activate because the input resistance was 22% lower and resting membrane potential was hyperpolarized 4.1 mV further below firing threshold (-50.9 +/- 6.2 mV). In acute spinal rats, during a slow voltage ramp, a PIC was activated subthreshold to the spike (at -57.2 +/- 5.0 mV) and reached a peak current of 1.11 +/- 1.21 nA. This PIC was less than one-half the size of that in chronic spinal rats (2.79 +/- 0.94 nA) and usually was not large enough to produce bistable behavior (plateau potentials and self-sustained firing not present), unlike in chronic spinal rats. The PIC was composed of two components: a TTX-sensitive Na PIC (0.44 +/- 0.36 nA) and a nimodipine-sensitive Ca PIC (0.78 +/- 0.82 nA). Both were smaller than in chronic spinal rats (but with similar Na/Ca ratio). The presence of the Na PIC was critical for normal repetitive firing, because no detectable Na PIC was found in the few motoneurons that could not fire repetitively during a slow ramp current injection and motoneurons that had large Na PICs more readily produced repetitive firing and had lower minimum firing rates compared with neurons with small Na PICs. Furthermore, when the Na PIC was selectively blocked with riluzole, steady repetitive firing was eliminated, even though transient firing could be evoked on a rapid current step and the spike itself was unaffected. In summary, only small Ca and Na PICs occur in acute spinal motoneurons, but the Na PIC is essential for steady repetitive firing. We discuss how availability of monoamines may explain the variability in Na PICs and firing in the normal and spinal animals.

Epidural Stimulation Induced Modulation of Spinal Locomotor Networks in Adult Spinal Rats

“…The latency of the first component of the late response recorded during standing corresponds to more then one synaptic delay , and epidural stimulation and afferent input from a moving treadmill facilitate the multiple spikes in late response, when each successive spike occurs at a latency of ϳ2 ms. We speculate that the multiple potentials of the late response reflect primarily variable numbers of synaptic events within the networks involved at any given phase of the step cycle. Other factors, such as repetitive firing of motoneurons that become more prominent after spinal cord injury (Harvey et al, 2006), also could contribute to these multiple components. Given that the late response is a composite response from a motor pool and therefore multiple motor units, it seems less likely that a regular interval between potentials would occur, given the relatively random nature of spike generation among motor units within a pool.…”

“…Given that the late response is a composite response from a motor pool and therefore multiple motor units, it seems less likely that a regular interval between potentials would occur, given the relatively random nature of spike generation among motor units within a pool. Also, the intervals between the components of the late response are ϳ2 ms, whereas a typical interval for action potentials within a single motor unit has been reported to be ϳ200 ms (Harvey et al, 2006). Other factors that could contribute to multiple potentials of late response may be the variation that must be inherent in the conduction velocities among the different afferents.…”

Inhibiting persistent inward sodium currents prevents myotonia

“…In motor neurons, repetitive firing is triggered by PICs, which are carried by both Na + and Ca + channels 16, 17, 18, 19. A NaPIC has been described previously in skeletal muscle20; this NaPIC lacked fast inactivation and activated between −80 and −70mV, such that it would convert a steady depolarization from K + buildup into myotonia.…”

“…Importantly, it also implies that NaPIC has a role in normal muscle function. One role of PICs in neurons is to convert steady depolarizations caused by the asynchronous firing of many weak synaptic inputs into repetitive spiking 16, 17, 18, 19. However, because skeletal muscle fibers receive only one synaptic input, there is no need for a PIC to convert multiple asynchronous synaptic firings into repetitive muscle APs.…”

“…In neurons, repetitive firing is maintained by persistent inward currents (PICs), which are activated by long depolarizations and mediated by Na + (Na + persistent inward current [NaPIC]) or Ca 2+ 16, 17, 18, 19. A NaPIC has also been described in wild‐type (WT) skeletal muscle 20.…”