Differential tetraethylammonium sensitivity of KCNQ1–4 potassium channels

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Abstract
In Shaker‐group potassium channels the presence of a tyrosine residue, just downstream of the pore signature sequence GYG, determines sensitivity to tetraethylammonium (TEA). The KCNQ family of channels has a variety of amino acid residues in the equivalent position. We studied the effect of TEA on currents generated by KCNQ homomers and heteromers expressed in CHO cells. We used wild‐type KCNQ1–4 channels and heteromeric KCNQ2/3 channels incorporating either wild‐type KCNQ3 subunits or a mutated KCNQ3 in which tyrosine replaced threonine at position 323 (mutant T323Y). IC50 values were (mM): KCNQ1, 5.0; KCNQ2, 0.3; KCNQ3, >30; KCNQ4, 3.0; KCNQ2+KCNQ3, 3.8; and KCNQ2+KCNQ3(T323Y), 0.5. While the high TEA sensitivity of KCNQ2 may be conferred by a tyrosine residue lacking in the other channels, the intermediate TEA sensitivity of KCNQ1 and KCNQ4 implies that other residues are also important in determining TEA block of the KCNQ channels. British Journal of Pharmacology (2000) 129, 413–415; doi:10.1038/sj.bjp.0703086