title: Opening and closing of KCNKO potassium leak channels is tightly regulated.
abstract: Potassium-selective leak channels control neuromuscular function through effects on membrane excitability. Nonetheless, their existence as independent molecular entities was established only recently with the cloning of KCNKO from Drosophila melanogaster. Here, the operating mechanism of these 2 P domain leak channels is delineated. Single KCNKO channels switch between two long-lived states (one open and one closed) in a tenaciously regulated fashion. Activation can increase the open probability to approximately 1, and inhibition can reduce it to approximately 0.05. Gating is dictated by a 700-residue carboxy-terminal tail that controls the closed state dwell time but does not form a channel gate; its deletion (to produce a 300-residue subunit with two P domains and four transmembrane segments) yields unregulated leak channels that enter, but do not maintain, the closed state. The tail integrates simultaneous input from multiple regulatory pathways acting via protein kinases C, A, and G.
authors.affiliation: Department of Pediatrics, Boyer Center for Molecular Medicine, Yale University School of Medicine, New Haven, Connecticut 06536, USA.
authors.forename: N
authors.initials: N
authors.lastname: Zilberberg
authors.forename: N
authors.initials: N
authors.lastname: Ilan
authors.forename: R
authors.initials: R
authors.lastname: Gonzalez-Colaso
authors.forename: S A
authors.initials: SA
authors.lastname: Goldstein
mesh_terms: D000818:Animals; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D017869:Cyclic GMP-Dependent Protein Kinases / Q000378:metabolism*; D004594:Electrophysiology; D015640:Ion Channel Gating / Q000502:physiology*; D016297:Mutagenesis, Site-Directed; D015221:Potassium Channels / Q000502:physiology*; D011493:Protein Kinase C / Q000378:metabolism*; D015398:Signal Transduction; D015854:Up-Regulation; D014982:Xenopus laevis
chemical_list: D015221:Potassium Channels; D017868:Cyclic AMP-Dependent Protein Kinases; D017869:Cyclic GMP-Dependent Protein Kinases; D011493:Protein Kinase C