Chemical and physical insults such as electroporation may compromise the membrane integrity and allow leak ion currents through de-novo formed lipid pores. These pores are thought to short-circuit the membrane and hinder ion channels' physiological function rather than to complement it. However, here we report that brief electric stimuli can trigger formation of membrane pores with specific behaviors that are traditionally considered to be unique for protein ion channels; still other behaviors of these pores distinguish them from both “conventional” electropores and any known ion channels. We found that a single electric shock (600-ns duration, 1 to 5 kV/cm) causes minutes-long increase of membrane electrical conductance due to formation of long-lived, voltage- and current-sensitive, rectifying, cation-selective, asymmetrical pores of nanometer diameter (“nanopores”). Once induced, nanopores oscillate between open and quasi-open (electrically silent) states, followed by either gradual resealing or abrupt breakdown into larger pores, with immediate loss of nanopore-specific behaviors. The formation and extended lifetime of nanopores were verified by non-electrophysiological methods, namely by fluorescent detection of Tl+ uptake and of phosphatidylserine externalization. Apparently, nanopores are not unique to cell stimulation with nanosecond electric pulses, but may form under various physiological and pathological conditions. Nanopores appear adequately equipped for certain functions that are traditionally ascribed to ion channels. Clear distinction between nanopores- and ion channels-mediated currents may be critical for understanding how these currents are controlled.Supported by NIH (NCI) R01CA125482.