Gating of voltage-dependent potassium channels

Activation of voltage-dependent ion channels is primarily controlled by the applied potential difference across the membrane. For potassium channels t he Drosophila Shaker channel has served as an archetype of all other potass ium channels in studies of activation mechanisms. In the Shaker potassium c hannel much of the voltage sensitivity is conferred by the S4 transmembrane helix, which contains seven positively charged residues. During gating, th e movement of these charges produces gating currents. Mutagenic and fluores cence studies indicate that four of these residues are particularly importa nt and contribute to the majority of gating charge, R362, R365, R368 and R3 71. The channel is thought to dwell in several closed states prior to openi ng. Ionic-charge pairing with negatively charged residues in the S2 and S3 helices is thought to be important in regulating these closed states and de tailed kinetic models have attempted to define the kinetics and charge of t he transitions between these states. Neutral residues throughout the S4 and S5 helices are thought to control late steps in channel opening and may ha ve important roles in modulating the stability of the open state and late c losed states. In response to depolarization, the S4 helix is thought to und ergo a rotational translation and this movement is also important in studie s of the movement of the pore helices, S5 and S6, during opening. This revi ew will examine residues that are important during activation as well as ki netic models that have attempted to quantitatively define the activation pa thway of voltage-dependent potassium channels. (C) 2001 Elsevier Science Lt d. All rights reserved.