Beauvericin activates Ca²⁺-activated Cl^- currents and induces cell deaths in Xenopus oocytes via influx of extracellular Ca ²⁺

Beauvericin is a mycotoxin that infects a wide variety of cereal grains. The toxicological importance of beauvericin is implicated by its cytotoxicity in animal and human cells, which has been suggested to result from an increase in intracellular Ca²⁺ concentration ([Ca²⁺]_i). Despite the fact that beauvericin may activate extracellular Ca²⁺ influx, beauvericin-induced cell deaths has been suggested to be exclusively due to Ca²⁺ release from internal Ca²⁺ stores. We endeavored to elucidate the mechanism of beauvericin-induced [Ca²⁺]_i increase by studying the effects of beauvericin in Xenopus oocytes. By applying a -140-mV prepulse prior to a series of test pulses, we found that beauvericin induced small inward currents at -140 mV, followed by outwardly rectifying currents that displayed an apparent reversal potential close to the expected equilibrium potential of Cl^-. Both the inward and outward currents induced by beauvericin were blocked by niflumic acid, a specific blocker for Ca²⁺-activated Cl^- currents (I_Cl,Ca) Removal of extracellular Ca²⁺, as well as perfusion of lanthanide, abrogated beauvericin-induced currents. Beauvericin also displayed prominent cytotoxic effects in Xenopus oocytes in a dose-dependent manner. In the absence of extracellular Ca²⁺, cytotoxicity-induced by 10 and 30 μM, but not 50 μM, of beauvericin was significantly diminished. Our results are consistent with the idea that beauvericin induces extracellular Ca²⁺ influx, which in turn activates I_Cl,Ca and contributes to beauvericin-induced cell deaths in Xenopus oocytes.