Differential Effects of Tityus bahiensis Scorpion Venom on Tetrodotoxin-Sensitive and Tetrodotoxin-Resistant Sodium Currents

Abstract

We examined modification of sodium channel gating by Tityus bahiensis scorpion venom (TbScV), and compared effects on native tetrodotoxin-sensitive and tetrodotoxin-resistant sodium currents from rat dorsal root ganglion neurons and cardiac myocytes. In neurons, TbScV dramatically reduced the rate of sodium current inactivation, increased current amplitude, and caused a negative shift in the voltage-dependence of activation and inactivation of tetrodotoxin-sensitive channels. Enhanced activation of modified sodium channels was independent of a depolarizing prepulse. We identified two components of neuronal tetrodotoxin-resistant current with biophysical properties similar to those described for NaV1.8 and NaV1.9. In contrast to its effects on neuronal tetrodotoxin-sensitive current, TbScV caused a small decrease in neuronal tetrodotoxin-resistant sodium current amplitude and the gating modifications described above were absent. A third tetrodotoxin-resistant current, NaV1.5 recorded in rat cardiac ventricular myocytes, was inhibited approximately 50% by TbScV, and the remaining current exhibited markedly slowed activation and inactivation. In conclusion, TbScV has very different effects on different sodium channel isoforms. Among the neuronal types, currents resistant to tetrodotoxin are also resistant to gating modification by TbScV. The cardiac tetrodotoxin-resistant current has complex sensitivity that includes both inhibition of current amplitude and slowing of activation and inactivation.

Neurotoxicity of Tityus bahiensis (brown scorpion) venom in sympathetic vas deferens preparations and neuronal cells

“…After incubating with T. bahiensis venom, the activation and the current–voltage curves were shifted to more negative potentials (to the left) and the current-peak amplitude increased. Similar results were reported with T. bahiensis venom using sensory dorsal root ganglia (DRG) neurons and ventricular cardiomyocytes (Moraes et al 2011 ). T. bahiensis venom also markedly reduced the rate of Na v -current inactivation in these cells (Moraes et al 2011 ).…”

Carvacrol modulates voltage-gated sodium channels kinetics in dorsal root ganglia

“…Isolation and cell culture of rat DRG neurons DRG neurons were obtained from the lumbar segments of 10 to 14-w old male Wistar rats (220-250 g body weight) using an enzymatic dissociation procedure as described previously (Joca et al, 2012;Moraes et al, 2011). Rats were rendered unconscious by exposure to CO 2 and decapitated.…”

Scorpion toxin peptide action at the ion channel subunit level

“…AmmVIII and AaH1 were found not to alter the Nav1.9 current in DRG neurons (Abbas et al, 2013). Recent publications have suggested that Tityus bahiensis scorpion venom (TbScV) (Moraes et al, 2011) and TsVII (Tityus serrulatus) (Gilchrist and Bosmans, 2012) have potential action on Nav1.8 and Nav1.9 channels, although this requires further assessment and characterization.…”