Modulation of Proton-Gated Channels by Antidepressants.

The chemical structures of some antidepressants are similar to those of recently described amine-containing ligands of acid-sensing ion channels (ASICs). ASICs are expressed in brain neurons and participate in numerous CNS functions. As such, they can be related to antidepressant action or side effects. We therefore studied the actions of a series of antidepressants on recombinant ASIC1a and ASIC2a and on native ASICs in rat brain neurons. Most of the tested compounds prevented steady-state ASIC1a desensitization evoked by conditioning acidification to pH 7.1. Amitriptyline also potentiated ASIC1a responses evoked by pH drops from 7.4 to 6.5. We conclude that amitriptyline has a twofold effect: it shifts activation to less acidic values while also shifting steady-state desensitization to more acidic values. Chlorpromazine, desipramine, amitriptyline, fluoxetine, and atomoxetine potentiated ASIC2a response. Tianeptine caused strong inhibition of ASIC2a. Both potentiation and inhibition of ASIC2a were accompanied by the slowdown of desensitization, suggesting distinct mechanisms of action on activation and desensitization. In experiments on native heteromeric ASICs, tianeptine and amitriptyline demonstrated the same modes of action as on ASIC2a although with reduced potency.

[1]  J. G. Rooney,et al.  Molecular basis of inhibition of acid sensing ion channel 1A by diminazene , 2018, PloS one.

[2]  F. Bihel,et al.  Heteroarylguanidines as Allosteric Modulators of ASIC1a and ASIC3 Channels. , 2018, ACS chemical neuroscience.

[3]  V. Pereira,et al.  A brief history of antidepressant drug development: from tricyclics to beyond ketamine , 2018, Acta Neuropsychiatrica.

[4]  D. Tikhonov,et al.  Potentiation and Block of ASIC1a by Memantine , 2018, Cellular and Molecular Neurobiology.

[5]  G. Rossetti,et al.  Diminazene Is a Slow Pore Blocker of Acid-Sensing Ion Channel 1a (ASIC1a) , 2017, Molecular Pharmacology.

[6]  M. S. Komarova,et al.  Complex action of tyramine, tryptamine and histamine on native and recombinant ASICs , 2017, Channels.

[7]  D. Tikhonov,et al.  Ligands of histamine receptors modulate acid-sensing ion channels. , 2017, Biochemical and biophysical research communications.

[8]  M. S. Komarova,et al.  TRPV1 activation power can switch an action mode for its polypeptide ligands , 2017, PloS one.

[9]  L. Rash Acid-Sensing Ion Channel Pharmacology, Past, Present, and Future …. , 2017, Advances in pharmacology.

[10]  L. Magazanik,et al.  Histamine selectively potentiates acid-sensing ion channel 1a , 2016, Neuroscience Letters.

[11]  L. Magazanik,et al.  Determinants of action of hydrophobic amines on ASIC1a and ASIC2a. , 2016, European journal of pharmacology.

[12]  Wei-Hsin Sun,et al.  Genetic exploration of the role of acid-sensing ion channels , 2015, Neuropharmacology.

[13]  M. S. Komarova,et al.  Non‐classical mechanism of α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid receptor channel block by fluoxetine , 2015, The European journal of neuroscience.

[14]  T. B. Tikhonova,et al.  Monoamine NMDA receptor channel blockers inhibit and potentiate native and recombinant proton-gated ion channels , 2015, Neuropharmacology.

[15]  L. Schild,et al.  International Union of Basic and Clinical Pharmacology. XCI. Structure, Function, and Pharmacology of Acid-Sensing Ion Channels and the Epithelial Na+ Channel , 2015, Pharmacological Reviews.

[16]  Caitlin V. Cosme,et al.  Acid-sensing ion channels contribute to synaptic transmission and inhibit cocaine-evoked plasticity , 2014, Nature Neuroscience.

[17]  M. Welsh,et al.  Protons are a neurotransmitter that regulates synaptic plasticity in the lateral amygdala , 2014, Proceedings of the National Academy of Sciences.

[18]  John A. Wemmie,et al.  Acid-sensing ion channels in pain and disease , 2013, Nature Reviews Neuroscience.

[19]  S. Hahn,et al.  Effects of fluoxetine on cloned Kv4.3 potassium channels , 2013, Brain Research.

[20]  Chih-Cheng Chen,et al.  Neurosensory mechanotransduction through acid-sensing ion channels , 2013, Journal of cellular and molecular medicine.

[21]  Dominique Douguet,et al.  Black mamba venom peptides target acid-sensing ion channels to abolish pain , 2012, Nature.

[22]  E. Vizi,et al.  GluN2B-containing NMDA receptors as possible targets for the neuroprotective and antidepressant effects of fluoxetine , 2012, Neurochemistry International.

[23]  Matthew A. Howard,et al.  The Amygdala Is a Chemosensor that Detects Carbon Dioxide and Acidosis to Elicit Fear Behavior , 2009, Cell.

[24]  A. Staruschenko,et al.  Mechanisms of non‐steroid anti‐inflammatory drugs action on ASICs expressed in hippocampal interneurons , 2008, Journal of neurochemistry.

[25]  John A. Wemmie,et al.  Targeting ASIC1a Reduces Innate Fear and Alters Neuronal Activity in the Fear Circuit , 2007, Biological Psychiatry.

[26]  E. Vizi,et al.  The Mechanism of Activity-Dependent Sodium Channel Inhibition by the Antidepressants Fluoxetine and Desipramine , 2006, Molecular Pharmacology.

[27]  H. Kalbacher,et al.  The Tarantula Toxin Psalmotoxin 1 Inhibits Acid-sensing Ion Channel (ASIC) 1a by Increasing Its Apparent H+ Affinity , 2005, The Journal of general physiology.

[28]  John A Wemmie,et al.  Overexpression of acid-sensing ion channel 1a in transgenic mice increases acquired fear-related behavior. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[29]  D. Min,et al.  Fluoxetine blocks cloned neuronal A-type K+ channels Kv1.4 , 2003, Neuroreport.

[30]  J. Fisher,et al.  Fluoxetine Increases GABAA Receptor Activity through a Novel Modulatory Site , 2003, Journal of Pharmacology and Experimental Therapeutics.

[31]  M. Lazdunski,et al.  ASIC‐like, proton‐activated currents in rat hippocampal neurons , 2002, The Journal of physiology.

[32]  Gero Miesenböck,et al.  Visualizing secretion and synaptic transmission with pH-sensitive green fluorescent proteins , 1998, Nature.

[33]  M. Lazdunski,et al.  Molecular Cloning of a Non-inactivating Proton-gated Na+ Channel Specific for Sensory Neurons* , 1997, The Journal of Biological Chemistry.

[34]  M. Lazdunski,et al.  A proton-gated cation channel involved in acid-sensing , 1997, Nature.

[35]  J. Gjessing Ketamine® (Cl‐581) in Clinical Anaesthesia , 1968, Acta anaesthesiologica Scandinavica.