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 ganglio n preparation, were used to investigate the role of tetrodotoxin-resis tant (TTX-R) afferent fibers in the sensory synaptic transmission in t he superficial DH. Bath application of 25-50 mM potassium to the DRG d epolarized the DRG neurons, blocked action potentials in the large neu rons, evoked action potentials in slow conducting neurons, and synapti cally excited dorsal horn neurons. Excitatory postsynaptic potentials (EPSP) which were evoked in DH neurons by electrical stimulation of la rge myelinated fibers, but not those evoked by stimulation of small un myelinated fibers, were blocked by the potassium treatment of the prim ary afferents. Tetrodotoxin, when applied to the sensory neurons, abol ished the action potentials in fast fibers but had no effect on the ac tion potentials in a population of slow conducting afferents. Peripher al application of TTX blocked the fast EPSPs evoked by electrical stim ulation 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. T his effect was abolished in Na+-free solution. These findings indicate that high [K+](e) applied to the DRG, dorsal root and peripheral proc ess selectively activates a primary afferent input to the DH, which is sodium-dependent and tetrodotoxin resistant.