VOCCs and TREK-1 ion channel expression in human tenocytes

2007 ◽  
Vol 292 (3) ◽  
pp. C1053-C1060 ◽  
Author(s):  
Merzesh Magra ◽  
Steven Hughes ◽  
Alicia J. El Haj ◽  
Nicola Maffulli
Keyword(s):  
Ion Channels ◽  
Ion Channel ◽  
Ionic Currents ◽  
Cell Types ◽  
Functional Expression ◽  
Tissue Cell ◽  
Pharmacological Management ◽  
Whole Cell ◽  
Voltage Gated ◽  
Channel Expression

Mechanosensitive and voltage-gated ion channels are known to perform important roles in mechanotransduction in a number of connective tissues, including bone and muscle. It is hypothesized that voltage-gated and mechanosensitive ion channels also may play a key role in some or all initial responses of human tenocytes to mechanical stimulation. However, to date there has been no direct investigation of ion channel expression by human tenocytes. Human tenocytes were cultured from patellar tendon samples harvested from five patients undergoing routine total knee replacement surgery (mean age: 66 yr; range: 63–73 yr). RT-PCR, Western blotting, and whole cell electrophysiological studies were performed to investigate the expression of different classes of ion channels within tenocytes. Human tenocytes expressed mRNA and protein encoding voltage-operated calcium channel (VOCC) subunits (Ca α1A, Ca α1C, Ca α1D, Ca α2δ1) and the mechanosensitive tandem pore domain potassium channel (2PK+) TREK-1. They exhibit whole cell currents consistent with the functional expression of these channels. In addition, other ionic currents were detected within tenocytes consistent with the expression of a diverse array of other ion channels. VOCCs and TREK channels have been implicated in mechanotransduction signaling pathways in numerous connective tissue cell types. These mechanisms may be present in human tenocytes. In addition, human tenocytes may express other channel currents. Ion channels may represent potential targets for the pharmacological management of chronic tendinopathies.

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 Neuromodulation independently determines correlated channel expression and conductance levels in motor neurons of the stomatogastric ganglion

2012 ◽  
Vol 107 (2) ◽  
pp. 718-727 ◽  
Author(s):  
Simone Temporal ◽  
Mohati Desai ◽  
Olga Khorkova ◽  
Gladis Varghese ◽  
Aihua Dai ◽  
...  
Keyword(s):  
Ion Channels ◽  
Motor Neurons ◽  
Ionic Current ◽  
Ionic Currents ◽  
Transcript Level ◽  
Ionic Channels ◽  
Cell Types ◽  
Synaptic Activity ◽  
Protein Levels ◽  
Channel Expression

Neuronal identity depends on the regulated expression of numerous molecular components, especially ionic channels, which determine the electrical signature of a neuron. Such regulation depends on at least two key factors, activity itself and neuromodulatory input. Neuronal electrical activity can modify the expression of ionic currents in homeostatic or nonhomeostatic fashion. Neuromodulators typically modify activity by regulating the properties or expression levels of subsets of ionic channels. In the stomatogastric system of crustaceans, both types of regulation have been demonstrated. Furthermore, the regulation of the coordinated expression of ionic currents and the channels that carry these currents has been recently reported in diverse neuronal systems, with neuromodulators not only controlling the absolute levels of ionic current expression but also, over long periods of time, appearing to modify their correlated expression. We hypothesize that neuromodulators may regulate the correlated expression of ion channels at multiple levels and in a cell-type-dependent fashion. We report that in two identified neuronal types, three ionic currents are linearly correlated in a pairwise manner, suggesting their coexpression or direct interactions, under normal neuromodulatory conditions. In each cell, some currents remain correlated after neuromodulatory input is removed, whereas the correlations between the other pairs are either lost or altered. Interestingly, in each cell, a different suite of currents change their correlation. At the transcript level we observe distinct alterations in correlations between channel mRNA amounts, including one of the cell types lacking a correlation under normal neuromodulatory conditions and then gaining the correlation when neuromodulators are removed. Synaptic activity does not appear to contribute, with one possible exception, to the correlated expression of either ionic currents or of the transcripts that code for the respective channels. We conclude that neuromodulators regulate the correlated expression of ion channels at both the transcript and the protein levels.

scholarly journals Functional Expression of TRPV1 Ion Channel in the Canine Peripheral Blood Mononuclear Cells

2021 ◽  
Vol 22 (6) ◽  
pp. 3177
Author(s):  
Joanna K. Bujak ◽  
Daria Kosmala ◽  
Kinga Majchrzak-Kuligowska ◽  
Piotr Bednarczyk
Keyword(s):  
Patch Clamp ◽  
Ion Channel ◽  
Peripheral Blood Mononuclear Cells ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Functional Expression ◽  
Peripheral Blood Mononuclear ◽  
Whole Cell ◽  
Whole Cell Patch Clamp ◽  
Blood Mononuclear Cells

TRPV1, known as a capsaicin receptor, is the best-described transient receptor potential (TRP) ion channel. Recently, it was shown to be expressed by non-excitable cells such as lymphocytes. However, the data regarding the functional expression of the TRPV1 channel in the immune cells are often contradictory. In the present study, we performed a phylogenetical analysis of the canine TRP ion channels, we assessed the expression of TRPV1 in the canine peripheral blood mononuclear cells (PBMC) by qPCR and Western blot, and we determined the functionality of TRPV1 by whole-cell patch-clamp recordings and calcium assay. We found high expression of TRPV2, -M2, and -M7 in the canine PBMCs, while expression of TRPV1, -V4 and, -M5 was relatively low. We confirmed that TRPV1 is expressed on the protein level in the PBMC and it localizes in the plasma membrane. The whole-cell patch-clamp recording revealed that capsaicin application caused a significant increase in the current density. Similarly, the results from the calcium assay show a dose-dependent increase in intracellular calcium level in the presence of capsaicin that was partially abolished by capsazepine. Our study confirms the expression of TRPV1 ion channel on both mRNA and protein levels in the canine PBMC and indicates that the ion channel is functional.

scholarly journals Ionic bases for electrical remodeling of the canine cardiac ventricle

2013 ◽  
Vol 305 (3) ◽  
pp. H410-H419 ◽  
Author(s):  
Darwin Jeyaraj ◽  
Xiaoping Wan ◽  
Eckhard Ficker ◽  
Julian E. Stelzer ◽  
Isabelle Deschenes ◽  
...  
Keyword(s):  
Ion Channels ◽  
Ion Channel ◽  
Phase 1 ◽  
Myocardial Strain ◽  
Ionic Currents ◽  
Left Ventricular ◽  
Electrical Remodeling ◽  
Cardiac Ventricle ◽  
Ionic Mechanisms ◽  
Ventricular Electrical Remodeling

Emerging evidence suggests that ventricular electrical remodeling (VER) is triggered by regional myocardial strain via mechanoelectrical feedback mechanisms; however, the ionic mechanisms underlying strain-induced VER are poorly understood. To determine its ionic basis, VER induced by altered electrical activation in dogs undergoing left ventricular pacing ( n = 6) were compared with unpaced controls ( n = 4). Action potential (AP) durations (APDs), ionic currents, and Ca2+ transients were measured from canine epicardial myocytes isolated from early-activated (low strain) and late-activated (high strain) left ventricular regions. VER in the early-activated region was characterized by minimal APD prolongation, but marked attenuation of the AP phase 1 notch attributed to reduced transient outward K+ current. In contrast, VER in the late-activated region was characterized by significant APD prolongation. Despite marked APD prolongation, there was surprisingly minimal change in ion channel densities but a twofold increase in diastolic Ca2+. Computer simulations demonstrated that changes in sarcolemmal ion channel density could only account for attenuation of the AP notch observed in the early-activated region but failed to account for APD remodeling in the late-activated region. Furthermore, these simulations identified that cytosolic Ca2+ accounted for APD prolongation in the late-activated region by enhancing forward-mode Na+/Ca2+ exchanger activity, corroborated by increased Na+/Ca2+ exchanger protein expression. Finally, assessment of skinned fibers after VER identified altered myofilament Ca2+ sensitivity in late-activated regions to be associated with increased diastolic levels of Ca2+. In conclusion, we identified two distinct ionic mechanisms that underlie VER: 1) strain-independent changes in early-activated regions due to remodeling of sarcolemmal ion channels with no changes in Ca2+ handling and 2) a novel and unexpected mechanism for strain-induced VER in late-activated regions in the canine arising from remodeling of sarcomeric Ca2+ handling rather than sarcolemmal ion channels.

BK Channels in Human Glioma Cells

2001 ◽  
Vol 85 (2) ◽  
pp. 790-803 ◽  
Author(s):  
Christopher B. Ransom ◽  
Harald Sontheimer
Keyword(s):  
Rank Order ◽  
Glioma Cells ◽  
Cell Types ◽  
Bk Channels ◽  
Human Glioma ◽  
Human Glioma Cells ◽  
Whole Cell ◽  
Channel Expression ◽  
Intracellular Ca ◽  
Current Activation

Ion channels in inexcitable cells are involved in proliferation and volume regulation. Glioma cells robustly proliferate and undergo shape and volume changes during invasive migration. We investigated ion channel expression in two human glioma cell lines (D54MG and STTG-1). With low [Ca2+]i, both cell types displayed voltage-dependent currents that activated at positive voltages (more than +50 mV). Current density was sensitive to intracellular cation replacement with the following rank order; K+ > Cs+ ≈ Li+ > Na+. Currents were >80% inhibited by iberiotoxin (33 nM), charybdotoxin (50 nM), quinine (1 mM), tetrandrine (30 μM), and tetraethylammonium ion (TEA; 1 mM). Extracellular phloretin (100 μM), an activator of BK(Ca2+) channels, and elevated intracellular Ca2+ negatively shifted the I-V curve of whole cell currents. With 0, 0.1, and 1 μM [Ca2+]i, the half-maximal voltages, V 0.5, for whole cell current activation were +150, +65, and +12 mV, respectively. Elevating [K+]o potentiated whole cell currents in a fashion proportional to the square-root of [K+]o. Recording from cell-attached patches revealed large conductance channels (150–200 pS) with similar voltage dependence and activation kinetics as whole cell currents. These data indicate that human glioma cells express large-conductance, Ca2+-activated K+ (BK) channels. In amphotericin-perforated patches bradykinin (1 μM) activated TEA-sensitive currents that were abolished by preincubation with bis-( o-aminophenoxy)- N,N,N′,N′-tetraacetic acid-AM (BAPTA-AM). The BK channels described here may influence the responses of glioma cells to stimuli that increase [Ca2+]i.

scholarly journals Cell Types, Network Homeostasis, and Pathological Compensation from a Biologically Plausible Ion Channel Expression Model

Neuron ◽  
2014 ◽  
Vol 82 (4) ◽  
pp. 809-821 ◽  
Author(s):  
Timothy O’Leary ◽  
Alex H. Williams ◽  
Alessio Franci ◽  
Eve Marder
Keyword(s):  
Ion Channel ◽  
Cell Types ◽  
Channel Expression ◽  
Expression Model

scholarly journals Plasma membrane ion channels and epithelial to mesenchymal transition in cancer cells

2016 ◽  
Vol 23 (11) ◽  
pp. R517-R525 ◽  
Author(s):  
Iman Azimi ◽  
Gregory R Monteith
Keyword(s):  
Plasma Membrane ◽  
Ion Channels ◽  
Ion Channel ◽  
Cancer Cells ◽  
Epithelial To Mesenchymal Transition ◽  
Therapeutic Resistance ◽  
Therapeutic Approaches ◽  
Mesenchymal Transition ◽  
Pharmacological Modulation ◽  
Channel Expression

A variety of studies have suggested that epithelial to mesenchymal transition (EMT) may be important in the progression of cancer in patients through metastasis and/or therapeutic resistance. A number of pathways have been investigated in EMT in cancer cells. Recently, changes in plasma membrane ion channel expression as a consequence of EMT have been reported. Other studies have identified specific ion channels able to regulate aspects of EMT induction. The utility of plasma membrane ion channels as targets for pharmacological modulation make them attractive for therapeutic approaches to target EMT. In this review, we provide an overview of some of the key plasma membrane ion channel types and highlight some of the studies that are beginning to define changes in plasma membrane ion channels as a consequence of EMT and also their possible roles in EMT induction.

scholarly journals Ion Channel Expression and Characterization in Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes

2018 ◽  
Vol 2018 ◽  
pp. 1-14 ◽  
Author(s):  
Zhihan Zhao ◽  
Huan Lan ◽  
Ibrahim El-Battrawy ◽  
Xin Li ◽  
Fanis Buljubasic ◽  
...  
Keyword(s):  
Stem Cell ◽  
Ion Channels ◽  
Ion Channel ◽  
Pluripotent Stem Cell ◽  
Induced Pluripotent Stem Cell ◽  
Biological Study ◽  
Adrenergic Stimulation ◽  
Cell Therapies ◽  
Channel Expression ◽  
Induced Pluripotent

Background. Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) are providing new possibilities for the biological study, cell therapies, and drug discovery. However, the ion channel expression and functions as well as regulations in hiPSC-CMs still need to be fully characterized. Methods. Cardiomyocytes were derived from hiPS cells that were generated from two healthy donors. qPCR and patch clamp techniques were used for the study. Results. In addition to the reported ion channels, INa, ICa-L, ICa-T, If, INCX, IK1, Ito, IKr, IKs IKATP, IK-pH, ISK1–3, and ISK4, we detected both the expression and currents of ACh-activated (KACh) and Na+-activated (KNa) K+, volume-regulated and calcium-activated (Cl-Ca) Cl−, and TRPV channels. All the detected ion currents except IK1, IKACh, ISK, IKNa, and TRPV1 currents contribute to AP duration. Isoprenaline increased ICa-L, If, and IKs but reduced INa and INCX, without an effect on Ito, IK1, ISK1–3, IKATP, IKr, ISK4, IKNa, ICl-Ca, and ITRPV1. Carbachol alone showed no effect on the tested ion channel currents. Conclusion. Our data demonstrate that most ion channels, which are present in healthy or diseased cardiomyocytes, exist in hiPSC-CMs. Some of them contribute to action potential performance and are regulated by adrenergic stimulation.

scholarly journals Ionflux: A Microfluidic Approach to Ensemble Recording and Block of Whole-Cell Current from Voltage-Gated Ion Channels

2010 ◽  
Vol 98 (3) ◽  
pp. 194a ◽  
Author(s):  
C. Ian Spencer ◽  
Nianzhen Li ◽  
Juliette Johnson ◽  
Qin Chen ◽  
Cristian Ionescu-Zanetti
Keyword(s):  
Ion Channels ◽  
Whole Cell ◽  
Voltage Gated ◽  
Cell Current ◽  
Voltage Gated Ion Channels ◽  
Whole Cell Current ◽  
Gated Ion Channels

Voltage-Gated Ion Channels and Hereditary Disease

1999 ◽  
Vol 79 (4) ◽  
pp. 1317-1372 ◽  
Author(s):  
Frank Lehmann-Horn ◽  
Karin Jurkat-Rott
Keyword(s):  
Ion Channels ◽  
Ion Channel ◽  
Recombinant Dna ◽  
Hereditary Disease ◽  
Hereditary Diseases ◽  
Technological Advancement ◽  
Myotonia Congenita ◽  
Voltage Gated ◽  
Voltage Gated Ion Channels ◽  
Gated Ion Channels

By the introduction of technological advancement in methods of structural analysis, electronics, and recombinant DNA techniques, research in physiology has become molecular. Additionally, focus of interest has been moving away from classical physiology to become increasingly centered on mechanisms of disease. A wonderful example for this development, as evident by this review, is the field of ion channel research which would not be nearly as advanced had it not been for human diseases to clarify. It is for this reason that structure-function relationships and ion channel electrophysiology cannot be separated from the genetic and clinical description of ion channelopathies. Unique among reviews of this topic is that all known human hereditary diseases of voltage-gated ion channels are described covering various fields of medicine such as neurology (nocturnal frontal lobe epilepsy, benign neonatal convulsions, episodic ataxia, hemiplegic migraine, deafness, stationary night blindness), nephrology (X-linked recessive nephrolithiasis, Bartter), myology (hypokalemic and hyperkalemic periodic paralysis, myotonia congenita, paramyotonia, malignant hyperthermia), cardiology (LQT syndrome), and interesting parallels in mechanisms of disease emphasized. Likewise, all types of voltage-gated ion channels for cations (sodium, calcium, and potassium channels) and anions (chloride channels) are described together with all knowledge about pharmacology, structure, expression, isoforms, and encoding genes.

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