Delayed-rectifier K+ Channels

This synopsis refers only to actions demonstrated within or close to therapeutic concentrations of drugs. Abbreviations (+) to (+++) weak to strong efficacy, (-) no efficacy, ( ) not investigated. HVA high threshold Ca2 channels, T T-type Ca2+ channels, L L-type Ca2+ channels, iNap persistent sodium current, DR delayed rectifier K channels, KCNQ KCNQ subtypes of K+ channels. 

Delayed-rectifier K+ channels activate with a delay and mediate outwardly-rectifying K+ currents. These channels may make a significant contribution to the icpolarizing phase of nervous action potentials. 

In this sense, we have observed that, unlike tamoxifen, the quaternary derivative ethylbromide tamoxifen fails to block volume-sensitive chloride channels (as those found in lens fibers) in HeLa and Cl300 neuroblastoma cells (unpublished data). Likewise, ethylbromide tamoxifen is totally ineffective on delayed rectifier K+ channels in NG108-15 cells, while tamoxifen is a potent reversible blocker (Allen et al. 2000). From this point of view, nonpermeant SERM derivatives are useful pharmacological tools for investigating whether binding sites in membrane targets are located in the extracellular domains of membrane proteins or, because they can partition into the membrane, interact at some level within the lipid bilayers. 

Spector, P.S., Curran, M.E., Keating, M. T. and Sanguinetti, M.C. (1996) Class III antiarrhyfhmic drugs block hERG, a human cardiac delayed rectifier K+ channel. Open channel block by methanesulfonalides. Circulation Research, 78, 499-503. 

Rampe, D., Wibble, B., Brown, A.M. and Dage, R.C. (1993) Effects of terfenadine and its metabolites on a delayed rectifier K+ channel doned from human heart. Molecular Pharmacology, 44, 1240-1245. 

Chadwick, C.C., Krafte, D.S., Oconnor, B., Volberg, W.A., Ezrin, A.M., Johnson, R.E. and Silver, P.J. (1995) Evidence for multiple antiarrhythmic binding-sites on the cardiac rapidly activating delayed rectifier K - - channel. Drug Development Research, 34, 376-380. 

The 5-HT4 receptors modulate the activities of channels and transporters by increasing cAMP levels. These include activation of L-type Ca2+ channels (326), chloride currents in human jejunal mucosa and rat distal colon (330,331), and the If pacemaker current in atrial myocytes (332) and stimulation of aldosterone release from the adrenal glands (333,334), striatal dopamine release (324), hippocampal and frontal cortex acetylcholine release (335,336), and hippocampal 5-HT release (337). 5-HT4 receptors also inhibit various channels, including a KV3.2-like delayed rectifier K+ channel (303), a voltage-activated K+ channel in colliculi neurons (320,338), a Ca2+-activated, afterhyperpolariz-ing, and K+ current in hippocampus (325). 

Spector PS, Curran ME, Keating MT, Sanguinetti MC. Class III antiarrhythmic drugs block HERG, a human cardiac delayed rectifier K+ channel Open-channel block by methanesulfonanilides. Circ Res 1996 78 499-503. 

Wang L, Feng ZP, Kondo CS, Sheldon RS, Ouff HJ. Developmental changes in the delayed rectifier K Channels in mouse heart. Circ Res 1996 79(1) 79-85. 

Honore E, Barhanin J, Attali B, Lesage F, Lazdunski M (1994) External blockade of the major cardiac delayed-rectifier K+ channel (Kvl.5) by polyunsaturated fatty acids. Proc Natl Acad Sci USA 91 1937-1941... 

Stricharts( What is the evidence that the passive properties for these very small processes with large surfaceivolume ratios are changed as a result of Na accumulation, affecting for example delayed rectifier K channels or Ca2 -activated K channels In most of the modelling, you assumed that the passive properties were invariant you just added an active process on top of that. 

Gubitosi-Klug RA, Gross RW. Fatty acid ethyl esters, nonoxidative metabolites of ethanol, accelerate the kinetics of activation of the human brain delayed rectifier K channel, Kv 1.1. J Biol Chem 1996 271 32,519-32,522. 

Voltage-Dependent (Ky) Transient Outward (fto) and Delayed Rectifier (/k) Channels... 

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