KCNKO: Single, cloned potassium leak channels are multi-ion pores

KCNKO was the first clone to show attributes of a leak conductance: voltage -independent potassium currents that develop without delay. Its novel produ ct is predicted to have two nonidentical P domains and four transmembrane s egments and to assemble in pairs. Here, the mechanistic basis for leak is e xamined at the single-channel level. KCNKO channels open at all voltages in bursts that last for minutes with open probability close to 1. The channel s also enter a minutes-long closed state in a tightly regulated fashion. KC NKO has a common relative permeability series (Eisenman type IV) but conduc ts only thallium and potassium readily. KCNKO exhibits concentration-depend ent unitary conductance, anomalous mole fraction behavior, and pore occlusi on by barium. These observations argue for ion-channel and ion-ion interact ions in a multi-ion pore and deny the operation of independence or constant -field current formulations. Despite their unique function and structure, l eakage channels are observed to operate like classical potassium channels f ormed with one-P-domain subunits.