scholarly journals Insights into the biophysical properties of GABAA ion channels: Modulation of ion permeation by drugs and protein interactions

2011 ◽  
Vol 1808 (3) ◽  
pp. 667-673 ◽  
Author(s):  
M. Louise Tierney
Keyword(s):  
Ion Channels ◽  
Protein Interactions ◽  
Ion Permeation ◽  
Biophysical Properties

scholarly journals TOK Homologue in Neurospora crassa: First Cloning and Functional Characterization of an Ion Channel in a Filamentous Fungus

2003 ◽  
Vol 2 (1) ◽  
pp. 181-190 ◽  
Author(s):  
Stephen K. Roberts
Keyword(s):  
Ion Channels ◽  
Ion Channel ◽  
Neurospora Crassa ◽  
Filamentous Fungus ◽  
Single Channel ◽  
Functional Characterization ◽  
Reversal Potential ◽  
Channel Activity ◽  
Biophysical Properties ◽  
Patch Clamp Technique

ABSTRACT In contrast to animal and plant cells, very little is known of ion channel function in fungal physiology. The life cycle of most fungi depends on the “filamentous” polarized growth of hyphal cells; however, no ion channels have been cloned from filamentous fungi and comparatively few preliminary recordings of ion channel activity have been made. In an attempt to gain an insight into the role of ion channels in fungal hyphal physiology, a homolog of the yeast K+ channel (ScTOK1) was cloned from the filamentous fungus, Neurospora crassa. The patch clamp technique was used to investigate the biophysical properties of the N. crassa K+ channel (NcTOKA) after heterologous expression of NcTOKA in yeast. NcTOKA mediated mainly time-dependent outward whole-cell currents, and the reversal potential of these currents indicated that it conducted K+ efflux. NcTOKA channel gating was sensitive to extracellular K+ such that channel activation was dependent on the reversal potential for K+. However, expression of NcTOKA was able to overcome the K+ auxotrophy of a yeast mutant missing the K+ uptake transporters TRK1 and TRK2, suggesting that NcTOKA also mediated K+ influx. Consistent with this, close inspection of NcTOKA-mediated currents revealed small inward K+ currents at potentials negative of EK. NcTOKA single-channel activity was characterized by rapid flickering between the open and closed states with a unitary conductance of 16 pS. NcTOKA was effectively blocked by extracellular Ca2+, verapamil, quinine, and TEA+ but was insensitive to Cs+, 4-aminopyridine, and glibenclamide. The physiological significance of NcTOKA is discussed in the context of its biophysical properties.

scholarly journals Deciphering the interactions of SARS-CoV-2 proteins with human ion channels using machine learning-based method

2021 ◽  
Author(s):  
Nupur S. Munjal ◽  
Dikscha Sapra ◽  
Abhishek Goyal ◽  
K.T. Shreya Parthasarathi ◽  
Akhilesh Pandey ◽  
...  
Keyword(s):  
Machine Learning ◽  
Ion Channels ◽  
Protein Interactions ◽  
Transient Receptor Potential ◽  
Trp Channels ◽  
Transmission Rate ◽  
Drug Repurposing ◽  
Receptor Potential ◽  
Ppi Networks ◽  
Approved Drugs

Abstract Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the worldwide COVID-19 pandemic which began in 2019. It has a high transmission rate and pathogenicity leading to health emergencies and economic crisis. Recent studies pertaining to the understanding of the molecular pathogenesis of SARS-CoV-2 infection exhibited the indispensable role of ion channels in viral infection inside the host. Moreover, machine learning-based algorithms are providing higher accuracy for host-SARS-CoV-2 protein-protein interactions (PPIs). In this study, predictions of PPIs of SARS-CoV-2 proteins with human ion channels (HICs) were performed using PPI-MetaGO algorithm. The PPIs were predicted with 82.71% accuracy, 84.09% precision, 84.09% sensitivity, 0.89 AUC-ROC, 65.17% MCC score and 84.09% F1 score. Thereafter, PPI networks of SARS-CoV-2 proteins with HICs were generated. Furthermore, biological pathway analysis of HICs interacting with SARS-CoV-2 proteins showed the involvement of six pathways, namely inflammatory mediator regulation of TRP channels, insulin secretion, renin secretion, gap junction, taste transduction and apelin signaling pathway. The inositol 1,4,5-trisphosphate receptor 1 (ITPR1) and transient receptor potential cation channel subfamily A member 1 (TRPA1) were identified as potential target proteins. Various FDA approved drugs interacting with ITPR1 and TRPA1 are also available. It is anticipated that targeting ITPR1 and TRPA1 may provide a better therapeutic management of infection caused by SARS-CoV-2. The study also reinforces the drug repurposing approach for the development of host directed antiviral drugs.

Ion Channel Permeation and Selectivity

2019 ◽  
Author(s):  
Juan J. Nogueira ◽  
Ben Corry
Keyword(s):  
Ion Channels ◽  
Ion Channel ◽  
Ion Selectivity ◽  
Ionic Currents ◽  
Biological Processes ◽  
Ion Permeation ◽  
Voltage Gated ◽  
Physical Mechanisms ◽  
Theoretical Approaches ◽  
Mechanistic Insight

Many biological processes essential for life rely on the transport of specific ions at specific times across cell membranes. Such exquisite control of ionic currents, which is regulated by protein ion channels, is fundamental for the proper functioning of the cells. It is not surprising, therefore, that the mechanism of ion permeation and selectivity in ion channels has been extensively investigated by means of experimental and theoretical approaches. These studies have provided great mechanistic insight but have also raised new questions that are still unresolved. This chapter first summarizes the main techniques that have provided significant knowledge about ion permeation and selectivity. It then discusses the physical mechanisms leading to ion permeation and the explanations that have been proposed for ion selectivity in voltage-gated potassium, sodium, and calcium channels.

scholarly journals Biophysical Properties of the Alternative Ion Permeation Pore in TRPM3

2015 ◽  
Vol 108 (2) ◽  
pp. 283a
Author(s):  
Katharina Held ◽  
Thomas Voets ◽  
Joris Vriens
Keyword(s):  
Ion Permeation ◽  
Biophysical Properties

scholarly journals Stomatin‐domain protein interactions with acid‐sensing ion channels modulate nociceptor mechanosensitivity

2013 ◽  
Vol 591 (22) ◽  
pp. 5555-5574 ◽  
Author(s):  
Rabih A. Moshourab ◽  
Christiane Wetzel ◽  
Carlos Martinez‐Salgado ◽  
Gary R. Lewin
Keyword(s):  
Ion Channels ◽  
Protein Interactions ◽  
Acid Sensing Ion Channels ◽  
Domain Protein

scholarly journals Role of lysophosphatidic acid in ion channel function and disease

2018 ◽  
Vol 120 (3) ◽  
pp. 1198-1211 ◽  
Author(s):  
Ileana Hernández-Araiza ◽  
Sara L. Morales-Lázaro ◽  
Jesús Aldair Canul-Sánchez ◽  
León D. Islas ◽  
Tamara Rosenbaum
Keyword(s):  
Ion Channels ◽  
Ion Channel ◽  
Lysophosphatidic Acid ◽  
Protein Interactions ◽  
Molecular Mechanisms ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Channel Function ◽  
Transient Receptor ◽  
Lipid Protein Interactions

Lysophosphatidic acid (LPA) is a bioactive phospholipid that exhibits a wide array of functions that include regulation of protein synthesis and adequate development of organisms. LPA is present in the membranes of cells and in the serum of several mammals and has also been shown to participate importantly in pathophysiological conditions. For several decades it was known that LPA produces some of its effects in cells through its interaction with specific G protein-coupled receptors, which in turn are responsible for signaling pathways that regulate cellular function. Among the target proteins for LPA receptors are ion channels that modulate diverse aspects of the physiology of cells and organs where they are expressed. However, recent studies have begun to unveil direct effects of LPA on ion channels, highlighting this phospholipid as a direct agonist and adding to the knowledge of the field of lipid-protein interactions. Moreover, the roles of LPA in pathophysiological conditions associated with the function of some ion channels have also begun to be clarified, and molecular mechanisms have been identified. This review focuses on the effects of LPA on ion channel function under normal and pathological conditions and highlights our present knowledge of the mechanisms by which it regulates the function and expression of N- and T-type Ca++ channels; M-type K+ channel and inward rectifier K+ channel subunit 2.1; transient receptor potential (TRP) melastatin 2, TRP vanilloid 1, and TRP ankyrin 1 channels; and TWIK-related K+ channel 1 (TREK-1), TREK-2, TWIK-related spinal cord K+ channel (TRESK), and TWIK-related arachidonic acid-stimulated K+ channel (TRAAK).

scholarly journals A generalized kinetic model describes ion-permeation mechanisms in various ion channels

2021 ◽  
Author(s):  
Di Wu
Keyword(s):  
Ion Channels ◽  
Kinetic Model ◽  
Patch Clamp ◽  
Cellular Responses ◽  
Ion Permeation ◽  
Patch Clamp Recording ◽  
Boltzmann Factor ◽  
Current Voltage ◽  
Test Voltage ◽  
Generalized Kinetic Model

Ion channels conduct various ions across biological membranes to maintain the membrane potential, to transmit the electrical signals, and to elicit the subsequent cellular responses by the signaling ions. Ion channels differ in their capabilities to select and conduct ions, which can be studied by the patch-clamp recording method that compares the current traces responding to the test voltage elicited at different conditions. In these experiments, the current-voltage curves are usually fitted by a sigmoidal function containing the Boltzmann factor. This equation is quite successful in fitting the experimental data in many cases, but it also fails in several others. Regretfully, some useful information may be lost in these data, which otherwise can reveal the ion-permeation mechanisms. Here we present a generalized kinetic model that captures the essential features of the current-voltage relations and describes the simple mechanism of the ion permeation through different ion channels. We demonstrate that this model is capable to fit various types of the patch-clamp data and explain their ion-permeation mechanisms.

scholarly journals Identification of TMEM206 proteins as pore of PAORAC/ASOR acid-sensitive chloride channels

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Florian Ullrich ◽  
Sandy Blin ◽  
Katina Lazarow ◽  
Tony Daubitz ◽  
Jens Peter von Kries ◽  
...  
Keyword(s):  
Cell Death ◽  
Plasma Membrane ◽  
Ion Channels ◽  
Gene Family ◽  
Chloride Channels ◽  
Anion Channel ◽  
Ion Permeation ◽  
Acid Sensing Ion Channels ◽  
Genome Wide ◽  
A Genome

Acid-sensing ion channels have important functions in physiology and pathology, but the molecular composition of acid-activated chloride channels had remained unclear. We now used a genome-wide siRNA screen to molecularly identify the widely expressed acid-sensitive outwardly-rectifying anion channel PAORAC/ASOR. ASOR is formed by TMEM206 proteins which display two transmembrane domains (TMs) and are expressed at the plasma membrane. Ion permeation-changing mutations along the length of TM2 and at the end of TM1 suggest that these segments line ASOR’s pore. While not belonging to a gene family, TMEM206 has orthologs in probably all vertebrates. Currents from evolutionarily distant orthologs share activation by protons, a feature essential for ASOR’s role in acid-induced cell death. TMEM206 defines a novel class of ion channels. Its identification will help to understand its physiological roles and the diverse ways by which anion-selective pores can be formed.

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