scholarly journals Microarray-Based Comparisons of Ion Channel Expression Patterns: Human Keratinocytes to Reprogrammed hiPSCs to Differentiated Neuronal and Cardiac Progeny

2013 ◽  
Vol 2013 ◽  
pp. 1-25 ◽  
Author(s):  
Leonhard Linta ◽  
Marianne Stockmann ◽  
Qiong Lin ◽  
André Lechel ◽  
Christian Proepper ◽  
...  
Keyword(s):  
Ion Channels ◽  
Ion Channel ◽  
Ion Selectivity ◽  
Expression Patterns ◽  
Stem Cell Differentiation ◽  
Human Keratinocytes ◽  
Ips Cells ◽  
Cellular Processes ◽  
Gating Mechanism ◽  
Channel Expression

Ion channels are involved in a large variety of cellular processes including stem cell differentiation. Numerous families of ion channels are present in the organism which can be distinguished by means of, for example, ion selectivity, gating mechanism, composition, or cell biological function. To characterize the distinct expression of this group of ion channels we have compared the mRNA expression levels of ion channel genes between human keratinocyte-derived induced pluripotent stem cells (hiPSCs) and their somatic cell source, keratinocytes from plucked human hair. This comparison revealed that 26% of the analyzed probes showed an upregulation of ion channels in hiPSCs while just 6% were downregulated. Additionally, iPSCs express a much higher number of ion channels compared to keratinocytes. Further, to narrow down specificity of ion channel expression in iPS cells we compared their expression patterns with differentiated progeny, namely, neurons and cardiomyocytes derived from iPS cells. To conclude, hiPSCs exhibit a very considerable and diverse ion channel expression pattern. Their detailed analysis could give an insight into their contribution to many cellular processes and even disease mechanisms.

scholarly journals Ion channel expression patterns in glioblastoma stem cells with functional and therapeutic implications for malignancy

PLoS ONE ◽  
2017 ◽  
Vol 12 (3) ◽  
pp. e0172884 ◽  
Author(s):  
Julia Pollak ◽  
Karan G. Rai ◽  
Cory C. Funk ◽  
Sonali Arora ◽  
Eunjee Lee ◽  
...  
Keyword(s):  
Stem Cells ◽  
Ion Channel ◽  
Expression Patterns ◽  
Glioblastoma Stem Cells ◽  
Therapeutic Implications ◽  
Channel Expression

scholarly journals Artificial Intelligence, Machine Learning and Deep Learning in Ion Channel Bioinformatics

Membranes ◽  
2021 ◽  
Vol 11 (9) ◽  
pp. 672
Author(s):  
Md. Ashrafuzzaman
Keyword(s):  
Artificial Intelligence ◽  
Machine Learning ◽  
Deep Learning ◽  
Ion Channels ◽  
Ion Channel ◽  
Research Trend ◽  
Cellular Processes ◽  
Research Areas ◽  
Huge Data ◽  
Functional Aspects

Ion channels are linked to important cellular processes. For more than half a century, we have been learning various structural and functional aspects of ion channels using biological, physiological, biochemical, and biophysical principles and techniques. In recent days, bioinformaticians and biophysicists having the necessary expertise and interests in computer science techniques including versatile algorithms have started covering a multitude of physiological aspects including especially evolution, mutations, and genomics of functional channels and channel subunits. In these focused research areas, the use of artificial intelligence (AI), machine learning (ML), and deep learning (DL) algorithms and associated models have been found very popular. With the help of available articles and information, this review provide an introduction to this novel research trend. Ion channel understanding is usually made considering the structural and functional perspectives, gating mechanisms, transport properties, channel protein mutations, etc. Focused research on ion channels and related findings over many decades accumulated huge data which may be utilized in a specialized scientific manner to fast conclude pinpointed aspects of channels. AI, ML, and DL techniques and models may appear as helping tools. This review aims at explaining the ways we may use the bioinformatics techniques and thus draw a few lines across the avenue to let the ion channel features appear clearer.

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 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 Application of rate-equilibrium free energy relationship analysis to nonequilibrium ion channel gating mechanisms

2009 ◽  
Vol 134 (2) ◽  
pp. 129-136 ◽  
Author(s):  
László Csanády
Keyword(s):  
Free Energy ◽  
Ion Channels ◽  
Transition State ◽  
Ion Channel ◽  
Conformational Transition ◽  
Limited Information ◽  
Relationship Analysis ◽  
Gating Mechanisms ◽  
Gating Mechanism ◽  
Transition State Structures

Rate-equilibrium free energy relationship (REFER) analysis provides information on transition-state structures and has been applied to reveal the temporal sequence in which the different regions of an ion channel protein move during a closed–open conformational transition. To date, the theory used to interpret REFER relationships has been developed only for equilibrium mechanisms. Gating of most ion channels is an equilibrium process, but recently several ion channels have been identified to have retained nonequilibrium traits in their gating cycles, inherited from transporter-like ancestors. So far it has not been examined to what extent REFER analysis is applicable to such systems. By deriving the REFER relationships for a simple nonequilibrium mechanism, this paper addresses whether an equilibrium mechanism can be distinguished from a nonequilibrium one by the characteristics of their REFER plots, and whether information on the transition-state structures can be obtained from REFER plots for gating mechanisms that are known to be nonequilibrium cycles. The results show that REFER plots do not carry information on the equilibrium nature of the underlying gating mechanism. Both equilibrium and nonequilibrium mechanisms can result in linear or nonlinear REFER plots, and complementarity of REFER slopes for opening and closing transitions is a trivial feature true for any mechanism. Additionally, REFER analysis provides limited information about the transition-state structures for gating schemes that are known to be nonequilibrium cycles.

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 Structural and molecular insight into the pH-induced low-permeability of the voltage-gated potassium channel Kv1.2 through dewetting of the water cavity

2019 ◽  
Author(s):  
Juhwan Lee ◽  
Mooseok Kang ◽  
Sangyeol Kim ◽  
Iksoo Chang
Keyword(s):  
Ion Channels ◽  
Ion Channel ◽  
Potassium Ion ◽  
Low Permeability ◽  
Voltage Gated ◽  
Kv Channels ◽  
Proton Concentration ◽  
Electrical Voltage ◽  
Gating Mechanism ◽  
Ph Dependent

AbstractUnderstanding the gating mechanism of ion channel proteins is key to understanding the regulation of cell signaling through these channels. Channel opening and closing are regulated by diverse environmental factors that include temperature, electrical voltage across the channel, and proton concentration. Low permeability in voltage-gated potassium ion channels (Kv) is intimately correlated with the prolonged action potential duration observed in many acidosis diseases. The Kv channels consist of voltage-sensing domains (S1–S4 helices) and central pore domains (S5–S6 helices) that include a selectivity filter and water-filled cavity. The voltage-sensing domain is responsible for the voltage-gating of Kv channels. While the low permeability of Kv channels to potassium ion is highly correlated with the cellular proton concentration, it is unclear how an intracellular acidic condition drives their closure, which may indicate an additional pH-dependent gating mechanism of the Kv family. Here, we show that two residues E327 and H418 in the proximity of the water cavity of Kv1.2 play crucial roles as a pH switch. In addition, we present a structural and molecular concept of the pH-dependent gating of Kv1.2 in atomic detail, showing that the protonation of E327 and H418 disrupts the electrostatic balance around the S6 helices, which leads to a straightening transition in the shape of their axes and causes dewetting of the water-filled cavity and closure of the channel. Our work offers a conceptual advancement to the regulation of the pH-dependent gating of various voltage-gated ion channels and their related biological functions.Author SummaryThe acid sensing ion channels are a biological machinery for maintaining the cell functional under the acidic or basic cellular environment. Understanding the pH-dependent gating mechanism of such channels provides the structural insight to design the molecular strategy in regulating the acidosis. Here, we studied the voltage-gated potassium ion channel Kv1.2 which senses not only the electrical voltage across the channels but also the cellular acidity. We uncovered that two key residues E327 and H418 in the pore domain of Kv1.2 channel play a role as pH-switch in that their protonation control the gating of the pore in Kv1.2 channel. It offered a molecular insight how the acidity reduces the ion permeability in voltage-gated potassium channels.

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.

scholarly journals Ion channel expression and electrophysiology of singular human (primary and induced pluripotent stem cell derived) cardiomyocytes

2021 ◽  
Author(s):  
Christina Schmid ◽  
Najah Abi-Gerges ◽  
Dietmar Zellner ◽  
Georg Rast
Keyword(s):  
Ion Channels ◽  
Action Potential ◽  
Ion Channel ◽  
Single Cell ◽  
Action Potential Duration ◽  
Drug Effects ◽  
Induced Pluripotent Stem Cell ◽  
Inward Current ◽  
Beat Rate ◽  
Channel Expression

SUMMARYHuman induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) and primary human cardiomyocytes are used for in vitro cardiac safety testing. hiPSC-CMs have been associated with a vast heterogeneity regarding single-cell morphology, beating behavior and action potential duration, prompting a systematic analysis of single-cell characteristics. Previously published hiPSC-CM studies revealed action potentials with nodal-, atrial- or ventricular-like morphology, although ion channel expression of singular hiPSC-CMs is not fully understood. Other studies used single-cell RNA-sequencing, however, these studies did not extensively focus on expression patterns of cardiac ion channels or failed to detect ion channel transcripts. Thus, the current study used a single-cell patch-clamp-RT-qPCR approach to get insights into single-cell electrophysiology (capacitance, action potential duration at 90% of repolarization, upstroke velocity, spontaneous beat rate, and sodium-driven fast inward current) and ion channel expression (HCN4, CACNA1G, CACNA1D, KCNA5, KCNJ4, SCN5A, KCNJ2, CACNA1D, and KCNH2), the combination of both within individual cells, and their correlations in single cardiomyocytes. We used commercially available hiPSC-CMs (iCell cardiomyocytes, atrial and ventricular Pluricytes) and primary human adult atrial and ventricular cardiomyocytes. Recordings of electrophysiological parameters revealed differences between the cell groups and variation within the hiPSC-CMs groups as well as within primary ventricular cardiomyocytes. Expression analysis on mRNA level showed no-clear-cut discrimination between primary cardiac subtypes and revealed both similarities and differences between all cell groups. Higher expression of atrial-associated ion channels in primary atrial cardiomyocytes and atrial Pluricytes compared to their ventricular counterpart indicates a successful chamber-specific hiPSC differentiation. Interpretation of correlations between the single-cell parameters was challenging, as the total data set is complex, particularly for parameters depending on multiple processes, like the spontaneous beat rate. Yet, for example, expression of SCN5A correlated well with the fast inward current amplitude for all three hiPSC-CM groups. To further enhance our understanding of the physiology and composition of the investigated hiPSC-CMs, we compared beating and non-beating cells and assessed distributions of single-cell data. Investigating the single-cell phenotypes of hiPSC-CMs revealed a combination of attributes which may be interpreted as a mixture of traits of different adult cardiac cell types: (i) nodal-related pacemaking attributes are spontaneous generation of action potentials and high HCN4 expression; and (ii) non-nodal attributes: cells have a prominent INa-driven fast inward current, a fast upstroke velocity and a high expression of SCN5A. In conclusion, the combination of nodal- and non-nodal attributes in single hiPSC-CMs may hamper the interpretation of drug effects on complex electrophysiological parameters like beat rate and action potential duration. However, the proven expression of specific ion channels enables the evaluation of drug effects on ionic currents in a more realistic environment than in recombinant systems.

Dynamic of Ion Channel Expression at the Plasma Membrane of Cardiomyocytes

2012 ◽  
Vol 92 (3) ◽  
pp. 1317-1358 ◽  
Author(s):  
Elise Balse ◽  
David F. Steele ◽  
Hugues Abriel ◽  
Alain Coulombe ◽  
David Fedida ◽  
...  
Keyword(s):  
Ion Channels ◽  
Ion Channel ◽  
Cardiac Myocytes ◽  
Cardiac Myocyte ◽  
Membrane Lipids ◽  
Current Knowledge ◽  
Small Gtpases ◽  
Molecular Organization ◽  
Cardiac Sarcolemma ◽  
Channel Expression

Cardiac myocytes are characterized by distinct structural and functional entities involved in the generation and transmission of the action potential and the excitation-contraction coupling process. Key to their function is the specific organization of ion channels and transporters to and within distinct membrane domains, which supports the anisotropic propagation of the depolarization wave. This review addresses the current knowledge on the molecular actors regulating the distinct trafficking and targeting mechanisms of ion channels in the highly polarized cardiac myocyte. In addition to ubiquitous mechanisms shared by other excitable cells, cardiac myocytes show unique specialization, illustrated by the molecular organization of myocyte-myocyte contacts, e.g., the intercalated disc and the gap junction. Many factors contribute to the specialization of the cardiac sarcolemma and the functional expression of cardiac ion channels, including various anchoring proteins, motors, small GTPases, membrane lipids, and cholesterol. The discovery of genetic defects in some of these actors, leading to complex cardiac disorders, emphasizes the importance of trafficking and targeting of ion channels to cardiac function. A major challenge in the field is to understand how these and other actors work together in intact myocytes to fine-tune ion channel expression and control cardiac excitability.

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