The effects of veratridine have been compared on tetrodotoxin-sensitive (TTXS) and tetrodotoxin-resistant (TTXR) voltage-gated sodium channels (VGSC) in rat dorsal root ganglion neurons. Veratridine caused a dose-dependent decrease in the peak amplitude of both TTXR and TTXS VGSC currents. When exposed to 25 microM veratridine, TTXS currents but not TTXR currents developed a clear persistent component. The deactivation of both TTXS and TTXR currents was slowed, as evidenced by the appearance of slowly decaying tail currents in voltage clamp records, but the slowing of deactivation was nearly 100 times greater for TTXS than for TTXR currents. Properties of the veratridine-modified VGSCs, derived from an analysis of the slow tail currents, were similar for both TTXS and TTXR in that the V50 for activation and the reversal potential were shifted to more negative potentials than control currents and by a similar amount for each. The relatively fast decay of veratridine-modified TTXR tail currents reflects a faster dissociation of veratridine from TTXR than from TTXS VGSCs. This difference probably underlies the lack of effect of veratridine on TTXR VGSCs in cells that are not voltage-clamped and undermines its value as a chemical activator of putative NaV1.8 TTXR channels.

1 We have studied the eects of prostaglandin E 2 (PGE 2 ) on action potential propagation in the isolated, desheathed vagus and saphenous nerves of rats using an extracellular grease gap recording method. 2 PGE 2 evoked a small depolarization of vagus nerves but had no eect on the stimulation threshold, size or latency of either the A wave (corresponding to conduction in A ®bres) or the C wave (corresponding to conduction in C ®bres) of the compound action potential (CAP) recorded from either vagus or saphenous nerves. 3 Lidocaine (0.01 ± 10 mM) reduced all components of the CAP of both vagus and saphenous nerves. PGE 2 had no signi®cant eect on the sensitivity of any component of the CAP to lidocaine. 4 Tetrodotoxin (TTX, 10 mM) blocked completely both the A wave and the C wave of the CAP in either vagus or saphenous nerves. 5 In saphenous nerve preparations the A wave was blocked by lower concentrations of TTX than the C wave or any component of the CAP in vagus nerve preparations which suggests that somatosensory A ®bres express a dierent sub-type of TTX-sensitive voltage-gated sodium channel (VGSC) than somatosensory C-®bres or visceral sensory ®bres. 6 Chemical activation of VGSCs with veratridine (10 or 50 mM) induced a depolarization in either nerve. The depolarization induced by 50 mM veratridine was blocked by 10 mM TTX. 7 Although TTX-insensitive VGSCs are expressed by some vagal and some somatosensory neurones they do not appear to be expressed functionally in the axons.

No abstract

No abstract

No abstract