title: Voltage-Dependent Gating: Novel Insights from KCNQ1 Channels.
abstract: Gating of voltage-dependent cation channels involves three general molecular processes: voltage sensor activation, sensor-pore coupling, and pore opening. KCNQ1 is a voltage-gated potassium (Kv) channel whose distinctive properties have provided novel insights on fundamental principles of voltage-dependent gating. 1) Similar to other Kv channels, KCNQ1 voltage sensor activation undergoes two resolvable steps; but, unique to KCNQ1, the pore opens at both the intermediate and activated state of voltage sensor activation. The voltage sensor-pore coupling differs in the intermediate-open and the activated-open states, resulting in changes of open pore properties during voltage sensor activation. 2) The voltage sensor-pore coupling and pore opening require the membrane lipid PIP2 and intracellular ATP, respectively, as cofactors, thus voltage-dependent gating is dependent on multiple stimuli, including the binding of intracellular signaling molecules. These mechanisms underlie the extraordinary KCNE1 subunit modification of the KCNQ1 channel and have significant physiological implications.
authors.affiliation: Department of Biomedical Engineering, Cardiac Bioelectricity and Arrhythmia Center and Center for the Investigation of Membrane Excitability Disorders, Washington University, St. Louis, Missouri. Electronic address: jcui@wustl.edu.
authors.forename: Jianmin
authors.initials: J
authors.lastname: Cui
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000595:Amino Acid Sequence; D055724:Electrophysiological Phenomena; D042541:Intracellular Space / Q000378:metabolism; D015640:Ion Channel Gating; D051657:KCNQ1 Potassium Channel / Q000737:chemistry / Q000378:metabolism*; D008969:Molecular Sequence Data; D016062:Porosity
chemical_list: D051657:KCNQ1 Potassium Channel; D000255:Adenosine Triphosphate