The Sea Anemone Toxins BgII and BgIII Prolong the Inactivation Time Course of the Tetrodotoxin-Sensitive Sodium Current in Rat Dorsal Root Ganglion Neurons

Abstract

We have characterized the effects of BgII and BgIII, two sea anemone peptides with almost identical sequences (they only differ by a single amino acid), on neuronal sodium currents using the whole-cell patch-clamp technique. Neurons of dorsal root ganglia of Wistar rats (P5-9) in primary culture (LeibovitzЈs L15 medium; 37°C, 95% air/5% CO 2 ) were used for this study (n ϭ 154). These cells express two sodium current subtypes: tetrodotoxin-sensitive (TTX-S; K i ϭ 0.3 nM) and tetrodotoxinresistant (TTX-R; K i ϭ 100 M). Neither BgII nor BgIII had significant effects on TTX-R sodium current. Both BgII and BgIII produced a concentration-dependent slowing of the TTX-S sodium current inactivation (IC 50 ϭ 4.1 Ϯ 1.2 and 11.9 Ϯ 1.4 M, respectively), with no significant effects on activation time course or current peak amplitude. For comparison, the concentration-dependent action of Anemonia sulcata toxin II (ATX-II), a well characterized anemone toxin, on the TTX-S current was also studied. ATX-II also produced a slowing of the TTX-S sodium current inactivation, with an IC 50 value of 9.6 Ϯ 1.2 M indicating that BgII was 2.3 times more potent than ATX-II and 2.9 times more potent than BgIII in decreasing the inactivation time constant ( h ) of the sodium current in dorsal root ganglion neurons. The action of BgIII was voltage-dependent, with significant effects at voltages below Ϫ10 mV. Our results suggest that BgII and BgIII affect voltage-gated sodium channels in a similar fashion to other sea anemone toxins and ␣-scorpion toxins.

The Effect of Recombinant Neurotoxins from the Sea Anemone Anthopleura sp. on Sodium Currents of Rat Cerebral Cortical Neurons

“…This result was consistent with the site-3 toxin (Salceda et al 2002(Salceda et al , 2006Benzinger et al 1997). For example, the sea anemone toxins BgII and BgIII prolong the inactivation time course of the tetrodotoxin-sensitive sodium current in dorsal root ganglion neurons.…”

Functional coupling between sodium-activated potassium channels and voltage-dependent persistent sodium currents in cricket Kenyon cells

“…The use of this and other toxins that prolong Na ϩ -channel inactivation such as BgII and BgIII (the toxins isolated from the sea anemone Bunodosoma granulifera; Bosmans et al 2002;Salceda et al 2002) and CgNa (the toxin isolated from the sea anemone Condylactis gigantea; Billen et al 2010;Ständker et al 2006) would further support the functional coupling between K Na channels and voltage-dependent persistent Na ϩ current in cricket Kenyon cells. Hage and Salkoff (2012) suggested that I Naf is not responsible for the activation of K Na channels because I KNa persists even when I Naf is eliminated or reduced by a depolarizing holding potential of Ϫ50 mV in tufted/mitral cells.…”

Neurochemical characterization of nervous elements innervating the body wall of earthworms (Lumbricus, Eisenia): immunohistochemical and pharmacological studies

“…21c). This high dose was used, because the TTX sensitivities of the voltagedependent sodium channels were different (Salceda et al 2002;Djouhri et al 2003); some types of channels (e.g. Na v 1.7 channels) required high concentrations of TTX to block their conduction, whereas others were resistant to TTX.…”