Royero Pedro, García Lisbeth, Rosales Arnaldo, D'Suze Gina, Sevcik Carlos, Castillo Cecilia
Unidad de Neurociencias, Instituto de Estudios Avanzados IDEA, Caracas, 1080, Venezuela; Depto. de Biología Celular, Universidad Simón Bolívar, Caracas, 1080, Venezuela.
Unidad de Neurociencias, Instituto de Estudios Avanzados IDEA, Caracas, 1080, Venezuela.
Toxicon. 2018 Sep 1;151:37-46. doi: 10.1016/j.toxicon.2018.06.083. Epub 2018 Jun 28.
Bactridine 2 (Bact-2) is an antibacterial toxin from Tityus discrepans venom which modifies isoforms 1.2, 1.4 and 1.6 voltage-dependent sodium (Na) channels. Bactridine-induced Na outflow in Yersinia enterocolitica was blocked by amiloride, suggesting that Bact-2 effect was mediated by an amiloride sensitive sodium channel. In this study we show that Bact-2 increases also an outward rectifying current in rat dorsal root ganglia (DRG) sensory neurons; therefore, the nature of the outward rectifying currents was characterized and then the effect of Bact-2 on these currents was studied. These currents are enhanced by amiloride, are decreased by Na when an outward pH gradient is present and its reversal potential coincides with that of a Cl/H exchanger, suggesting that rectifying currents are produced by the electrogenic Cl/H exchanger modulated by the Na/H antiporter. Bact-2 also leads to an increase of the outward currents in a similar way to the produced by the inhibition of the Na/H exchanger. Additionally, the subsequent application of Bact-2 after blocking the Na/H exchanger does not produce any further effect, suggesting that Bact-2 modifies the outward current by modulating the activity of the Na/H exchanger. The effect of Bact-2 on pH regulation was determined using the pH indicator BCECF. The results show that the Na/H exchanger is blocked by amiloride and Na free solutions and is modulated by Bact-2 in a similar way as cariporide. This study validates that besides Na channels, Bact-2 modulates the activity of the Na/H exchanger.
杆菌肽2（Bact-2）是一种来自差异毒蝎毒液的抗菌毒素，它可修饰1.2、1.4和1.6亚型的电压依赖性钠（Na）通道。在小肠结肠炎耶尔森菌中，杆菌肽诱导的Na外流被氨氯地平阻断，这表明Bact-2的作用是由氨氯地平敏感的钠通道介导的。在本研究中，我们发现Bact-2还能增加大鼠背根神经节（DRG）感觉神经元中的外向整流电流；因此，我们对外向整流电流的性质进行了表征，然后研究了Bact-2对这些电流的影响。这些电流被氨氯地平增强，当存在外向pH梯度时被Na降低，其反转电位与Cl/H交换体的反转电位一致，这表明整流电流是由Na/H反向转运体调节的电生性Cl/H交换体产生的。Bact-2也以类似于抑制Na/H反向转运体所产生的方式导致外向电流增加。此外，在阻断Na/H反向转运体后随后应用Bact-2不会产生任何进一步的影响，这表明Bact-2通过调节Na/H反向转运体的活性来改变外向电流。使用pH指示剂BCECF测定了Bact-2对pH调节的影响。结果表明，Na/H反向转运体被氨氯地平和无Na溶液阻断，并被Bact-2以与卡里波罗德类似的方式调节。本研究证实，除了Na通道外，Bact-2还能调节Na/H反向转运体的活性。
