Block of L-Type Ca²⁺ Current by Beauvericin, a Toxic Cyclopeptide, in the NG108-15 Neuronal Cell Line

Abstract

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 microM) reversibly produced an inhibition of L-type voltage-dependent Ca2+ current (I(Ca,L)) in a concentration-dependent manner. Beauvericin caused no change in the overall shape of the current-voltage relationship of I(Ca,L). The IC(50) value of beauvericin-induced inhibition of I(Ca,L) was 4 microM. Neither gabapentin (30 microM) nor omega-conotoxin GVIA (3 microM) had effects on I(Ca,L). Beauvericin (30 microM) shifted the steady-state inactivation curve of I(Ca,L) to more negative membrane potentials by approximately -15 mV. The inhibitory effects of beauvericin on I(Ca,L) exhibited tonic and use-dependent characteristics. Beauvericin also suppressed I(Ca,L) evoked by repetitive action potential waveforms effectively. However, beauvericin (30 microM) 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.