Differential effect of Androctonus australis hector venom components on macrophage K_V channels: electrophysiological...

Neurotoxins of scorpion venoms modulate ion channels. Voltage-gated potassium (K_V) channels regulate the membrane potential and are involved in the activation and proliferation of immune cells. Macrophages are key components of the inflammatory response induced by scorpion venom. The present study was undertaken to investigate the effect of Androctonus australis hector (Aah) venom on K_V channels in murine resident peritoneal macrophages. The cytotoxicity of the venom was assessed using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) -based assay and electrophysiological recordings were performed using the whole-cell patch clamp technique. High doses of Aah venom (50, 125, 250 and 500 µg/ml) significantly decreased cell viability, while concentrations of 0.1-25 µg/ml were not cytotoxic towards peritoneal macrophages. Electrophysiological data revealed a differential block of K_V current between resting and LPS-activated macrophages. Aah venom significantly reduced K_V current amplitude by 62.5 ± 4.78% (n = 8, p < 0.05), reduced the use-dependent decay of the current, decreased the degree of inactivation and decelerated the inactivation process of K_V current in LPS-activated macrophages. Unlike cloned K_V1.5 channels, Aah venom exerted a similar blocking effect on K_V1.3 compared to K_V current in LPS-activated macrophages, along with a hyperpolarizing shift in the voltage dependence of K_V1.3 inactivation, indicating a direct mechanism of current inhibition by targeting K_V1.3 subunits. The obtained results, demonstrating that Aah venom differentially targets K_V channels in macrophages, suggest differential outcomes for their inhibitions, and that further investigations of scorpion venom immunomodulatory potential are required.