Tetrodotoxin-resistant sodium channels Na v1.8/SNS and Na v1.9/NaN in afferent neurons innervating urinary bladder in control and spinal cord injured rats

Abstract

Tetrodotoxin-resistant (TTX-R) sodium channels Na v1.8/SNS and Na v1.9/NaN are preferentially expressed in small diameter dorsal root ganglia (DRG) neurons. The urinary bladder is innervated by small afferent neurons from L6/S1 DRG, of which ∼75% exhibit high-threshold action potentials that are mediated by TTX-R sodium channels. Following transection of the spinal cord at T8, the bladder becomes areflexic and then gradually hyper-reflexic, and there is an attenuation of the TTX-R sodium currents in bladder afferent neurons. In the present study, we demonstrate that Na v1.8 is expressed in both bladder and non-bladder afferent neurons, while Na v1.9 is expressed in non-bladder afferent neurons but is rarely observed in bladder afferent neurons. In spinal cord transected rats 28–32 days following transection, there is a decreased expression of Na v1.8 sodium channels in bladder afferents, but no change in the expression of Na v1.8 in non-bladder afferent neurons. Both bladder and non-bladder afferent neurons exhibit limited increases in Na v1.9 expression following spinal cord transection. These results demonstrate that the expression of TTX-R channels in bladder afferent neurons changes after spinal cord transection, and these changes may contribute to the increased excitability of these neurons following spinal cord injury.