Electrostatic Tuning of Ion Conductance in Potassium Channels

Members of the K+ channel family display remarkable conservation of sequence and structure of the ion selectivity filter, whereas the rates of K+ turnover vary widely within the family. Here we show that channel conductance is strongly influenced by charge at the channel's intracellular mouth. Introduction of a ring of negative charges at this position in KcsA, a bacterial K+ channel, augments the conductance in a pH-dependent manner. These results are explained by a simple electrostatic effect based on known channel structures, where the negative charges serve to alter the electrical potential at the inner mouth and, thus, to increase the local K+ concentration. In addition, removal of the conserved negative charges at equivalent positions in a high-conductance eukaryotic K+ channel leads to a decrease in conductance.