Influence of outer pore residue K533 on the inhibition of Kv1.4 potassium channels by n -alkyl sulphate anions

We have previously shown that although n -octyl sulphate (OS – ) and n -dodecyl sulphate (DDS – ) anions had similar effects on the kinetics and activation voltage dependence of RCK1 (Kv1.1), RCK4 (Kv1.4) and Shaker B channels expressed in Xenopus oocytes, both compounds produced a large decrease in the maximum conductance of RCK4 channels while significantly increasing the conductance of RCK1 and Shaker B. We suggested that this channel-specific inhibition might depend on the nature of the amino-acid residue corresponding to position 533 in RCK4. We now present data on the effects of n -alkyl sulphates on an RCK4 mutant in which the wild-type lysine at position 533 was changed to the corresponding tyrosine residue in RCK1. At a concentration of 15 µM, DDS – caused a 48% reduction in the wild-type current at 50 mV but a 32% increase in the mutant current. n -Hexyl sulphate and OS – had similar differential effects. The activation and inactivation kinetics of the mutant current were still accelerated by n -alkyl sulphates and 15 µM DDS – moved the conductance/voltage curves of both wild-type and mutant channels some 24 mV in the hyperpolarizing direction. The K533Y mutation thus had a selective effect on current inhibition by n -alkyl sulphates.