title: Mg²⁺ modulation of the single-channel properties of KCa3.1 in human erythroleukemia cells.
abstract: The activity of many ion channels is modulated by ions other than the ones they primarily conduct, with important consequences for cell signalling. In this study, we demonstrate that Mg(2+) inhibits the intermediate conductance calcium-activated potassium channel (KCa3.1) in human erythroleukemia cells via two distinct mechanisms. Firstly, intracellular Mg(2+) blocks this channel via a rapid, voltage-dependent mechanism that leads to a reduction of the channel's unitary current. We show that this block involves interactions which are well described by the Woodhull model. Secondly, we found that Mg(2+) reduces the open probability of the channel. By analysing the channel kinetics, we found that this reduction in open probability is at least partly due to a reduction in the rate of channel opening from the closed state, a finding that can be accounted for if Mg(2+) competes with Ca(2+) for the activation site. Consistent with this interpretation, we find that the decline in relative NPo observed in the presence of 5 mM Mg(2+) could be significantly reduced by increasing the free Ca(2+) concentration.
authors.affiliation: Department of Physiology, Development and Neuroscience, University of Cambridge, Downing Street, Cambridge, CB2 3EG, UK.
authors.forename: Colin J
authors.initials: CJ
authors.lastname: Stoneking
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Mason
mesh_terms: D045744:Cell Line, Tumor; D006801:Humans; D015640:Ion Channel Gating; D007700:Kinetics; D051037:Large-Conductance Calcium-Activated Potassium Channel alpha Subunits / Q000378:metabolism*; D008274:Magnesium / Q000378:metabolism*; D008564:Membrane Potentials / Q000502:physiology*; D018408:Patch-Clamp Techniques
chemical_list: D051037:Large-Conductance Calcium-Activated Potassium Channel alpha Subunits; D008274:Magnesium