The actions of two omega-conopeptides on high-voltage-activated calcium channel currents in differentiated human neuroblastoma IMR32 cells were investigated. Similar to the previously reported action of omega-conopeptide GVIA, omega-conopeptide MVIIA irreversibly blocks IMR32 HVA calcium channel currents at low concentrations. Unlike GVIA action, however, novel omega-conopeptide SNX-260 (iodinated MVIIC) reversibly blocks these currents, also at low concentrations, with an IC50 near 50 nM. Different omega-conopeptides may be potent blockers of HVA calcium channel currents yet act either reversibly or irreversibly in a single cell.