Related Experiment Video

Updated: May 31, 2026

Radiosynthesis of 1-(2-[18F]Fluoroethyl)-L-Tryptophan using a One-pot, Two-step Protocol
08:33

Radiosynthesis of 1-(2-[18F]Fluoroethyl)-L-Tryptophan using a One-pot, Two-step Protocol

Published on: September 21, 2021

TREK-1 isoforms generated by alternative translation initiation display different susceptibility to the

Michaela Eckert1, Brigitte Egenberger, Frank Döring

  • 1Institute of Physiology, University of Würzburg, Würzburg, Germany.

Neuropharmacology
|July 12, 2011
PubMed

Insights

Fluoxetine, an antidepressant, potently inhibits TREK-1, a brain and cardiac potassium channel. Specific protein variants of TREK-1 show altered drug sensitivity, highlighting the importance of its N-terminal region.

Area of Science:

  • Neuroscience
  • Cardiology
  • Molecular Biology

Background:

  • Two-pore-domain potassium (K(2)P) channels are crucial in neuronal and cardiac function.
  • Understanding drug interactions with these channels is vital for therapeutic development.

Purpose of the Study:

  • To investigate the inhibitory effects of fluoxetine on brain and cardiac K(2)P channels, specifically TREK-1, TASK-1, and THIK-1.
  • To elucidate the role of alternative translation initiation in TREK-1 function and drug sensitivity.

Main Methods:

  • HEK-293 cell and Xenopus oocyte expression systems.
  • Electrophysiological analysis of wild-type and mutated TREK-1 channels.
  • Site-directed mutagenesis to generate TREK-1 variants (TREK-1[M53I], TREK-1[ΔN52]).

Main Results:

  • Fluoxetine maximally inhibited TREK-1 channels by 77%.
  • Alternative translation initiation of TREK-1 produces isoforms with altered current amplitude and K(+) selectivity.
  • The TREK-1[ΔN52] isoform exhibited a 70% decrease in fluoxetine sensitivity, indicating the N-terminus is critical for drug interaction.

Conclusions:

  • Fluoxetine is a potent inhibitor of TREK-1 channels.
  • The N-terminal region of TREK-1, specifically the first 52 amino acids, is essential for its sensitivity to fluoxetine.
  • Alternative translation initiation significantly impacts TREK-1 channel function and drug response.

More Related Videos

Toeprinting Analysis of Translation Initiation Complex Formation on Mammalian mRNAs10:37

Toeprinting Analysis of Translation Initiation Complex Formation on Mammalian mRNAs

Published on: May 10, 2018

Quantitative Immunofluorescence to Measure Global Localized Translation09:13

Quantitative Immunofluorescence to Measure Global Localized Translation

Published on: August 22, 2017

Related Concept Videos

Antidepressant Drugs: Tricyclics, SSRIs, and SNRIs01:28

Antidepressant Drugs: Tricyclics, SSRIs, and SNRIs

Tricyclic Antidepressants (TCAs), including Desipramine (Norpramin), Imipramine (Tofranil), Clomipramine (Anafranil), and Amitriptyline (Elavil), inhibit serotonin and norepinephrine reuptake and also block other receptors. They are used for depression, pain conditions, and insomnia. Common adverse effects include anticholinergic effects, sedation, orthostatic hypotension, and weight gain. They have a narrow therapeutic window and so require plasma-level monitoring. Abrupt discontinuation can...
Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase01:11

Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase

Genetic polymorphisms in drug targets have emerged as critical determinants of interindividual variability in drug response and toxicity. Pharmacogenomic investigations increasingly focus on identifying these variations to personalize and optimize therapeutic interventions. A drug target may be a receptor, enzyme, or signaling protein involved in pharmacologic responses or disease-related pathways. While early pharmacogenetic studies focused primarily on drug metabolism, current research...
Antidepressant Drugs: MAOIs and Other Agents01:23

Antidepressant Drugs: MAOIs and Other Agents

Atypical antidepressants, including bupropion (Wellbutrin), mirtazapine (Remeron), nefazodone (Serzone), trazodone (Desyrel), and vilazodone (Viibryd), offer unique mechanisms of action. Bupropion weakly inhibits dopamine and norepinephrine reuptake, aiding depression treatment and smoking cessation, with a low risk of sexual dysfunction. Mirtazapine enhances serotonin and norepinephrine neurotransmission, leading to sedation, increased appetite, and weight gain. As a result, it helps treat...
Antidepressant Drugs: Overview01:25

Antidepressant Drugs: Overview

Antidepressant drugs are a class of medications primarily used for treating various mood disorders, including major depression, anxiety disorders, and other related conditions. These medicines work by modulating the neurotransmitter balance within the brain, alleviating depressive symptoms. Antidepressants can be broadly categorized into several groups according to their mechanism of action and chemical structure: Selective Serotonin Reuptake Inhibitors (SSRIs), Serotonin-Norepinephrine...
Leaky Scanning02:28

Leaky Scanning

During most eukaryotic translation processes, the small 40S ribosome subunit scans an mRNA from its 5' end until it encounters the first start AUG codon. The large 60S ribosomal subunit then joins the smaller one to initiate protein synthesis. The location of the translation initiation is largely determined by the nucleotides near the start codon as there may be multiple translation initiation sites present on the mRNA.  Marilyn Kozak discovered that the sequence RCCAUGG (where R stands for...
Drugs Affecting GI Tract Motility: Serotonin Receptor Agonists01:23

Drugs Affecting GI Tract Motility: Serotonin Receptor Agonists

Serotonin, a crucial neurotransmitter synthesized by enterochromaffin cells, plays a cardinal role in regulating gastrointestinal (GI) motility. With over 90% of the body's total serotonin in the GI tract, its influence on digestive processes is profound. Serotonin is swiftly released upon various stimuli, such as food boluses or certain drugs, triggering intrinsic sensory neurons in the myenteric plexus and extrinsic vagal and spinal sensory neurons. This leads to the activation of the...