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Interaction Between Tetraethylammonium And Amino Acid Residues In The Pore Of Cloned Voltage-Dependent Potassium Channels, Michael Kavanaugh, Michael D. Varnum, Peregrine B. Osborne, Macdonald J. Christie, Andreas E. Busch, John P. Adelman, R. Alan North

Biomedical and Pharmaceutical Sciences Faculty Publications

Extracellular tetraethylammonium (TEA) inhibits currents in Xenopus oocytes that have been injected with mRNAs encoding voltage-dependent potassium channels. Concentration-response curves were used to measure the affinity of TEA; this differed up to 700-fold among channels RBK1 (KD 0.3 mM), RGK5 (KD 11 mM), and RBK2 (KD greater than 200 mM). Studies in which chimeric channels were expressed localized TEA binding to the putative extracellular loop between trans-membrane domains S5 and S6. Site-directed mutagenesis of residues in this region identified the residue Tyr379 of RBK1 as a crucial determinant of TEA sensitivity; substitution of Tyr in the equivalent positions of RBK2 …