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

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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 (Leibovitz′s L15 medium; 37°C, 95% air/5% CO2) were used for this study (n = 154). These cells express two sodium current subtypes: tetrodotoxin-sensitive (TTX-S; Ki = 0.3 nM) and tetrodotoxin-resistant (TTX-R;Ki = 100 μM). 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 (IC50 = 4.1 ± 1.2 and 11.9 ± 1.4 μM, 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 IC50 value of 9.6 ± 1.2 μM 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 (τh) of the sodium current in dorsal root ganglion neurons. The action of BgIII was voltage-dependent, with significant effects at voltages below −10 mV. Our results suggest that BgII and BgIII affect voltage-gated sodium channels in a similar fashion to other sea anemone toxins and α-scorpion toxins.