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Br J Pharmacol
1999 Dec 01;1287:1609-15. doi: 10.1038/sj.bjp.0702955.
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Inhibition of neuronal KV potassium currents by the antidepressant drug, fluoxetine.
Yeung SY, Millar JA, Mathie A.
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1. The effect of the antidepressant drug, fluoxetine on neuronal delayed rectifier (KV) potassium (K) currents was investigated using perforated-patch whole-cell electrophysiological recording methods. 2. Fluoxetine was an effective inhibitor of KV currents in cerebellar granule neurons (CGNs) and also inhibited recombinant KV1.1 channels expressed in Chinese hamster ovary (CHO) cells. 3. Fluoxetine had an IC50 of 11 microM in CGNs but was slightly less potent on KV1.1 channels (IC50=55 microM). Interestingly, fluoxetine was a much more potent inhibitor of KV1.1 expressed in mammalian cells than has been found previously for the same homomeric channel expressed in Xenopus oocytes. 4. At concentrations that produced around 50% block, the shape of the KV currents in the presence of fluoxetine was simply scaled down when compared to control currents. 5. The effect of fluoxetine on KV currents in CGNs was neither voltage-dependent nor dependent on the channels being in their open state. Both of these observations suggest that fluoxetine does not act as a simple open channel blocking agent. 6. It is concluded that block of KV currents in mammalian neurons can occur at therapeutic levels of fluoxetine. This could lead to an increase in neuronal excitability and this effect may contribute to the therapeutic antidepressant action of fluoxetine.
Altamura,
Clinical pharmacokinetics of fluoxetine.
1994, Pubmed
Altamura,
Clinical pharmacokinetics of fluoxetine.
1994,
Pubmed Armstrong,
Voltage-gated ion channels and electrical excitability.
1998,
Pubmed Bardoni,
Modifications of A-current kinetics in mammalian central neurones induced by extracellular zinc.
1994,
Pubmed Cull-Candy,
Voltage-activated membrane currents in rat cerebellar granule neurones.
1989,
Pubmed Farrugia,
Modulation of ionic currents in isolated canine and human jejunal circular smooth muscle cells by fluoxetine.
1996,
Pubmed French,
Blockage of squid axon potassium conductance by internal tetra-N-alkylammonium ions of various sizes.
1981,
Pubmed Galeotti,
Effect of potassium channel modulators in mouse forced swimming test.
1999,
Pubmed Hahn,
Inhibition by fluoxetine of voltage-activated ion channels in rat PC12 cells.
1999,
Pubmed Jalonen,
Single-channel and whole-cell currents in rat cerebellar granule cells.
1990,
Pubmed Karson,
Human brain fluoxetine concentrations.
1993,
Pubmed Kues,
Heterogeneous Expression Patterns of Mammalian Potassium Channel Genes in Developing and Adult Rat Brain.
1992,
Pubmed Kuo,
Imipramine inhibition of transient K+ current: an external open channel blocker preventing fast inactivation.
1998,
Pubmed Lavoie,
Atypical antidepressants inhibit depolarization-induced calcium uptake in rat hippocampus synaptosomes.
1997,
Pubmed Lev,
Protein tyrosine kinase PYK2 involved in Ca(2+)-induced regulation of ion channel and MAP kinase functions.
1995,
Pubmed Maertens,
Block by fluoxetine of volume-regulated anion channels.
1999,
Pubmed Mathie,
Voltage-activated potassium channels in mammalian neurons and their block by novel pharmacological agents.
1998,
Pubmed Pancrazio,
Inhibition of neuronal Na+ channels by antidepressant drugs.
1998,
Pubmed Rae,
Effect of Prozac on whole cell ionic currents in lens and corneal epithelia.
1995,
Pubmed Reeve,
Blockade of delayed rectifier K+ currents in neuroblastoma x glioma hybrid (NG 108-15) cells by clofilium, a class III antidysrhythmic agent.
1992,
Pubmed Robertson,
Pharmacology of a cloned potassium channel from mouse brain (MK-1) expressed in CHO cells: effects of blockers and an 'inactivation peptide'.
1993,
Pubmed Roeper,
Presynaptic potassium channels.
1996,
Pubmed Rudy,
Diversity and ubiquity of K channels.
1988,
Pubmed Sanguinetti,
Potassium channelopathies.
1997,
Pubmed Tytgat,
Effect of fluoxetine on a neuronal, voltage-dependent potassium channel (Kv1.1).
1997,
Pubmed
,
Xenbase Veh,
Immunohistochemical localization of five members of the Kv1 channel subunits: contrasting subcellular locations and neuron-specific co-localizations in rat brain.
1995,
Pubmed Watkins,
A non-inactivating K+ current sensitive to muscarinic receptor activation in rat cultured cerebellar granule neurons.
1996,
Pubmed Watkins,
Modulation of the gating of the transient outward potassium current of rat isolated cerebellar granule neurons by lanthanum.
1994,
Pubmed Wooltorton,
Potent block of potassium currents in rat isolated sympathetic neurones by the uncharged form of amitriptyline and related tricyclic compounds.
1995,
Pubmed Wooltorton,
Block of potassium currents in rat isolated sympathetic neurones by tricyclic antidepressants and structurally related compounds.
1993,
Pubmed Yeung,
Inhibition of neuronal KV potassium currents by the antidepressant drug, fluoxetine.
1999,
Pubmed
,
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