The effect of the electrical charge or the size of tile amino acid residue at the pore center of a slowly activation component of the delayed rectifier potassium channel: KCNQ1 was studied. K+ currents were measured after transfection of one of four KCNQ1 mutants: substituting Isoleucine with Lysine, Glutamate, Valine or Glycine and then transfected in COS-7 cells. Both the negatively- and positive charged residue 1313 K and 1313 E showed a loss of function when expressed alone and a dominant negative suppression when co-expressed with wild type KCNQ1. When the Site Was Substituted with the smallest neutral amino acid residue: 1313G, there was a small reduction of current when transfected alone and a gain of function when co-transfected with the wild type. 1313V showed no difference from the wild type. Changes of amino acid residue at the pore center of KCNQ1 may alter the channel function but this depends on tile electrical charge or the size of amino acid residue. (C) 2008 Elsevier Inc. All rights reserved.