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 microM, 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 microM 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.
MacDonald
S
S
Department of Anatomy and Physiology, University of Dundee, Dundee DD1 4HN, Scotland, UK.
Elliott
A A
AA
Harrold
J A
JA
Elliott
J R
JR
D000818:Animals; D000838:Anions / Q000737:chemistry / Q000378:metabolism*; D051665:Kv1.4 Potassium Channel / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D008239:Lysine / Q000737:chemistry / Q000378:metabolism*; D009865:Oocytes / Q000166:cytology / Q000502:physiology; D018408:Patch-Clamp Techniques; D026902:Potassium Channel Blockers / Q000737:chemistry / Q000378:metabolism*; D013431:Sulfates / Q000737:chemistry / Q000378:metabolism*; D019789:Tetraethylammonium / Q000378:metabolism; D014982:Xenopus laevis
D000838:Anions; D051665:Kv1.4 Potassium Channel; D026902:Potassium Channel Blockers; D013431:Sulfates; D019789:Tetraethylammonium; D008239:Lysine