Block of L-type Ca2+ current by beauvericin, a toxic cyclopeptide, in the NG108-15 neuronal cell line

The effects of beauverficin, a cyclodepsipeptide compound, on ion currents in a mouse neuroblastoma and rat glioma hybrid cell line, NG108-15, were investigated with the aid of the whole-cell voltage-clamp technique. Beauvericin (0.3-100 muM) reversibly produced an inhibition of L-type voltage-dependent Call current (I-Ca,I-L) in a concentration-dependent manner. Beauvericin caused no change in the overall shape of the current-voltage relationship of ICa,L. The IC50 value of beauvericin-induced inhibition of I-Ca,I-L was 4 muM. Neither gabapentin (30 muM) nor omega-conotoxin GVIA (3 muM) had effects on I-Ca,I-L. Beauvericin (30 muM) shifted the steady-state inactivation curve of I-Ca,I-L to more negative membrane potentials by approximately -15 mV. The inhibitory effects of beauvericin on ICa,L exhibited tonic and use-dependent characteristics. Beauvericin also suppressed I-Ca,I-L evoked by repetitive action potential waveforms effectively. However, beauvericin (30 muM) had no effect on delayed rectifier K+ current in NG105-18 cells. Under current-clamp configuration, beauvericin reduced the firing frequency of action potentials. Therefore, this study indicates that beauvericin is a relatively specific inhibitor of L-type Ca2+ current in NG108-15 cells.