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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
1997-3-28
pubmed:abstractText
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 in Xenopus 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 in Vg 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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0026-895X
pubmed:author
pubmed:issnType
Print
pubmed:volume
51
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
475-83
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1997
pubmed:articleTitle
Voltage-dependent inhibition of RCK1 K+ channels by phenol, p-cresol, and benzyl alcohol.
pubmed:affiliation
Department of Anatomy and Physiology, University of Dundee, Scotland.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't