PT  - JOURNAL ARTICLE
AU  - A. A. Elliott
AU  - J. R. Elliott
TI  - Voltage-Dependent Inhibition of RCK1 K<sup>+</sup> Channels by Phenol, <em>p</em>-Cresol, and Benzyl Alcohol
DP  - 1997 Mar 01
TA  - Molecular Pharmacology
PG  - 475--483
VI  - 51
IP  - 3
4099  - http://molpharm.aspetjournals.org/content/51/3/475.short
4100  - http://molpharm.aspetjournals.org/content/51/3/475.full
SO  - Mol Pharmacol1997 Mar 01; 51
AB  - Phenol has various medical applications but can cause convulsions and cardiac arrhythmia suggestive of K+ channel block. We examined phenol inhibition of the delayed-rectifier RCK1 (Kv1.1) K+ channel cloned from rat brain and expressed inXenopus laevis oocytes. Phenol (2.5 mm) caused a 43 ± 5 mV depolarizing shift in the RCK1 half-activation voltage (Vg) but only a 10 ± 3% decrease in the peak conductance at 80 mV. The 10–90% rise time was slightly increased, but this was not simply the result of the activation shift. By contrast, deactivation kinetics at −40 mV were greatly accelerated. The importance of the phenolic hydroxyl group was assessed by comparing the effects of p-cresol (a phenol) and its structural isomer benzyl alcohol (an aryl alcohol).p-Cresol (1.5 mm) produced a 53 ± 2 mV depolarizing shift in Vg, but benzyl alcohol was much less effective—20 mm caused a depolarizing shift of only 23 ± 1 mV. Both isomers also accelerated channel deactivation. Phenol and p-cresol are better hydrogen bond donors than acceptors, whereas benzyl alcohol is a better acceptor than donor. A hydrogen bond between the phenolic hydroxyl and a presently unknown acceptor group may therefore underlie some aspects of K+ channel inhibition. Depolarizing shifts inVg and accelerated tail kinetics are consistent with 1) preferential phenol binding to resting channels, causing the shift in Vg, and 2) a conducting phenol-bound open state with faster deactivation kinetics than the unbound open state. The American Society for Pharmacology and Experimental Therapeutics