Mg²⁺ modulation of the single-channel properties of KCa3.1 in human erythroleukemia cells.

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.