Abstract
In addition to a fast activating and immediately inactivating inward sodium current, many types of excitable cells possess a noninactivating or slowly inactivating component: the persistent sodium current (INaP). The INaP is found in normal primary sensory neurons where it is mediated by tetrodotoxin-sensitive sodium channels. The dorsal root ganglion (DRG) is the gateway for ectopic impulses that originate in pathological pain signals from the periphery. However, the role of INaP in DRG neurons remains unclear, particularly in neuropathic pain states. Using in vivo recordings from single medium- and large-diameter fibers isolated from the compressed DRG in Sprague-Dawley rats, we show that local application of riluzole, which blocks the INaP, also inhibits the spontaneous activity of A-type DRG neurons in a dose-dependent manner. Significantly, riluzole also abolished subthreshold membrane potential oscillations (SMPOs), although DRG neurons still responded to intracellular current injection with a single full-sized spike. In addition, the INaP was enhanced in medium- and large-sized neurons of the compressed DRG, while bath-applied riluzole significantly inhibited the INaP without affecting the transient sodium current (INaT). Taken together, these results demonstrate for the first time that the INaP blocker riluzole selectively inhibits INaP and thereby blocks SMPOs and the ectopic spontaneous activity of injured A-type DRG neurons. This suggests that the INaP of DRG neurons is a potential target for treating neuropathic pain at the peripheral level.
Highlights
Voltage-dependent sodium channels are responsible for the generation and conduction of action potentials in the membranes of excitable cells
In the present study we demonstrate that behavioral changes in rats undergoing a chronic compression of the dorsal root ganglion (CCD) [24,25] are concurrent with a significant enhancement of inactivating component: the persistent sodium current (INaP), along with its associated subthreshold membrane potential oscillations (SMPOs) and ectopic spotaneous activity (SA), in the correspondingly injured A-type DRG neurons
The INaP is enhanced in medium- and large-sized DRG neurons of the compressed DRG
Summary
Voltage-dependent sodium channels are responsible for the generation and conduction of action potentials in the membranes of excitable cells. INaP is critical to neuronal excitability, the modulation of nearthreshold membrane potentials, the amplification of synaptic currents, and the facilitation of repetitive firing [7,8,9,10]. It has been reported that INaP participates in epileptic firing in the central nervous system [5]. Among such cells as mesencephalic trigeminal sensory neurons and hippocampal neurons, INaP is considered to be one of the threshold currents modulating neuronal excitability under both physiological and pathological conditions
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