The role of tetrodotoxin-resistant sodium channels of small primary afferent fibers.

Intracellular recordings from neurons in the dorsal root ganglion (DRG) and dorsal horn (DH), in an in vitro spinal cord-dorsal root ganglion preparation, were used to investigate the role of tetrodotoxin-resistant (TTX-R) afferent fibers in the sensory synaptic transmission in the superficial DH. Bath application of 25-50 mM potassium to the DRG depolarized the DRG neurons, blocked action potentials in the large neurons, evoked action potentials in slow conducting neurons, and synaptically excited dorsal horn neurons. Excitatory postsynaptic potentials (EPSP) which were evoked in DH neurons by electrical stimulation of large myelinated fibers, but not those evoked by stimulation of small unmyelinated fibers, were blocked by the potassium treatment of the primary afferents. Tetrodotoxin, when applied to the sensory neurons, abolished the action potentials in fast fibers but had no effect on the action potentials in a population of slow conducting afferents. Peripheral application of TTX blocked the fast EPSPs evoked by electrical stimulation but failed to block the electrically evoked slow EPSPs and the synaptic activation of DH neurons induced by the application of high potassium to sensory neurons. Furthermore, high potassium potentiated electrically evoked, TTX-resistant EPSPs in the majority of neurons. This effect was abolished in Na(+)-free solution. These findings indicate that high [K+]e applied to the DRG, dorsal root and peripheral process selectively activates a primary afferent input to the DH, which is sodium-dependent and tetrodotoxin resistant.