scholarly journals Calnexin revealed as an ether-a-go-go chaperone by getting mutant worms up and going

2018 ◽  
Vol 150 (8) ◽  
pp. 1059-1061
Author(s):  
Jonathan T. Pierce
Keyword(s):  
Ion Channels ◽  
Dynamic Control ◽  
Cell Types ◽  
K Channel ◽  
Membrane Domains ◽  
Excitable Cells ◽  
Patch Clamp Recording ◽  
Cell Excitability ◽  
Distinct Membrane

The role of ion channels in cell excitability was first revealed in a series of voltage clamp experiments by Hodgkin and Huxley in the 1950s. However, it was not until the 1970s that patch-clamp recording ushered in a revolution that allowed physiologists to witness how ion channels flicker open and closed at angstrom scale and with microsecond resolution. The unexpectedly tight seal made by the patch pipette in the whole-cell configuration later allowed molecular biologists to suck up the insides of identified cells to unveil their unique molecular contents. By refining these techniques, researchers have scrutinized the surface and contents of excitable cells in detail over the past few decades. However, these powerful approaches do not discern which molecules are responsible for the dynamic control of the genesis, abundance, and subcellular localization of ion channels. In this dark territory, teams of unknown and poorly understood molecules guide specific ion channels through translation, folding, and modification, and then they shuttle them toward and away from distinct membrane domains via different subcellular routes. A central challenge in understanding these processes is the likelihood that these diverse regulatory molecules may be specific to ion channel subtypes, cell types, and circumstance. In work described in this issue, Bai et al. (2018. J. Gen. Physiol. https://doi.org/10.1085/jgp.201812025) begin to shed light on the biogenesis of UNC-103, a K+ channel found in Caenorhabditis elegans.

scholarly journals Development of a Novel Automated Ion Channel Recording Method Using “Inside-Out” Whole-Cell Membranes

2005 ◽  
Vol 10 (8) ◽  
pp. 806-813 ◽  
Author(s):  
Dmitry V. Vasilyev ◽  
Thomas L. Merrill ◽  
Mark R. Bowlby
Keyword(s):  
Ion Channels ◽  
Parallel Implementation ◽  
Drug Application ◽  
K Channel ◽  
Positive Pressure ◽  
Screening Methods ◽  
Patch Clamp Recording ◽  
Whole Cell ◽  
Cell Configuration ◽  
Inside Out

Efforts to develop novelmethods for recording from ion channels have been receiving increased attention in recent years. In this study, the authors report a unique “inside-out” whole-cell configuration of patch-clamp recording that has been developed. This method entails adding cells into a standard patch pipette and, with positive pressure, obtaining a gigaseal recording from a cell at the inside tip of the electrode. In this configuration, the cellmay be moved through the air, first rupturing part of the cellularmembrane and enabling bath access to the intracellular side of the membrane, and then into a series of wells containing differing solutions, enabling robotic control of all the steps in an experiment. The robotic system developed here fully automates the electrophysiological experiments, including gigaseal formation, obtaining whole-cell configuration, data acquisition, and drug application. Proof-of-principle experiments consisting of application of intracellularly acting potassium channel blockers to K+ channel cell lines resulted in a very rapid block, aswell as block reversal, of the current. This technique allows compound application directly to the intracellular side of ion channels and enables the dissociation of compound inactivities due to cellular barrier limitations. This technique should allow for parallel implementation of recording pipettes and the future development of larger array-based screening methods.

Actin dynamics as critical ion channel regulator: ENaC and Piezo in focus

2021 ◽  
Author(s):  
Elena A. Morachevskaya ◽  
Anastasia V. Sudarikova
Keyword(s):  
Ion Channels ◽  
Ion Channel ◽  
Dynamic Balance ◽  
Cell Volume Regulation ◽  
Actin Dynamics ◽  
Actin Binding ◽  
Actin Assembly ◽  
Excitable Cells ◽  
Physiological Processes

Ion channels in plasma membrane play a principal role in different physiological processes, including cell volume regulation, signal transduction and modulation of membrane potential in living cells. Actin-based cytoskeleton, which exists in a dynamic balance between monomeric and polymeric forms (globular and fibrillar actin), can be directly or indirectly involved in various cellular responses including modulation of ion channel activity. In this mini-review, we present an overview of the role of submembranous actin dynamics in the regulation of ion channels in excitable and non-excitable cells. Special attention is focused on the important data about the involvement of actin assembly/disassembly and some actin-binding proteins in the control of the Epithelial Na+ Channel (ENaC) and mechanosensitive Piezo channels whose integral activity has potential impact on membrane transport and multiple coupled cellular reactions. Growing evidence suggests that actin elements of the cytoskeleton can represent a "converging point" of various signaling pathways modulating the activity of ion transport proteins in cell membranes.

Targeting of membrane transporters in renal epithelia: when cell biology meets physiology

2000 ◽  
Vol 278 (2) ◽  
pp. F192-F201 ◽  
Author(s):  
Dennis Brown
Keyword(s):  
Epithelial Cells ◽  
Cell Biology ◽  
Cell Types ◽  
Coat Proteins ◽  
Membrane Domains ◽  
Cellular Functions ◽  
Sorting Signals ◽  
The Many ◽  
Different Cell Types

Epithelial cells in the kidney have highly specialized transport mechanisms that differ among the many tubule segments, and among the different cell types that are present in some regions. The purpose of this brief review is to examine some of the major intracellular mechanisms by which the membrane proteins that participate in these differentiated cellular functions are addressed, sorted, and delivered to specific membrane domains of epithelial cells. Unraveling these processes is important not only for our understanding of normal cellular function but is also critical for the interpretation of pathophysiological dysfunction in the context of newly generated molecular and cellular information concerning hereditary and acquired transporter abnormalities. Among the topics covered are sorting signals on proteins, role of the cytoskeleton, vesicle coat proteins, the fusion machinery, and exo- and endocytosis of recycling proteins. Examples of these events in renal epithelial cells are highlighted throughout this review and are related to the physiology of the kidney.

scholarly journals Bioelectric State and Cell Cycle Control of Mammalian Neural Stem Cells

2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
Julieta Aprea ◽  
Federico Calegari
Keyword(s):  
Stem Cells ◽  
Membrane Potential ◽  
Ion Channels ◽  
Neural Stem Cells ◽  
Current Knowledge ◽  
Cell Cycle Control ◽  
Resting Membrane Potential ◽  
Excitable Cells ◽  
Proliferation And Differentiation

The concerted action of ion channels and pumps establishing a resting membrane potential has been most thoroughly studied in the context of excitable cells, most notably neurons, but emerging evidences indicate that they are also involved in controlling proliferation and differentiation of nonexcitable somatic stem cells. The importance of understanding stem cell contribution to tissue formation during embryonic development, adult homeostasis, and regeneration in disease has prompted many groups to study and manipulate the membrane potential of stem cells in a variety of systems. In this paper we aimed at summarizing the current knowledge on the role of ion channels and pumps in the context of mammalian corticogenesis with particular emphasis on their contribution to the switch of neural stem cells from proliferation to differentiation and generation of more committed progenitors and neurons, whose lineage during brain development has been recently elucidated.

scholarly journals Molecular structure of human KATP in complex with ATP and ADP

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Kenneth Pak Kin Lee ◽  
Jue Chen ◽  
Roderick MacKinnon
Keyword(s):  
Regulatory Element ◽  
Katp Channels ◽  
Inward Rectifier ◽  
K Channel ◽  
Excitable Cells ◽  
Binding Domains ◽  
Inhibitory Site ◽  
Atp Inhibition ◽  
Adenosine Nucleotides

In many excitable cells, KATP channels respond to intracellular adenosine nucleotides: ATP inhibits while ADP activates. We present two structures of the human pancreatic KATP channel, containing the ABC transporter SUR1 and the inward-rectifier K+ channel Kir6.2, in the presence of Mg2+ and nucleotides. These structures, referred to as quatrefoil and propeller forms, were determined by single-particle cryo-EM at 3.9 Å and 5.6 Å, respectively. In both forms, ATP occupies the inhibitory site in Kir6.2. The nucleotide-binding domains of SUR1 are dimerized with Mg2+-ATP in the degenerate site and Mg2+-ADP in the consensus site. A lasso extension forms an interface between SUR1 and Kir6.2 adjacent to the ATP site in the propeller form and is disrupted in the quatrefoil form. These structures support the role of SUR1 as an ADP sensor and highlight the lasso extension as a key regulatory element in ADP’s ability to override ATP inhibition.

scholarly journals The Role of K+ And Ca2+ Ion Channels in Α-Terpinyle Acetate-Induced Vasodilation in Rat’s Aortic Rings

2017 ◽  
Vol 5 (2) ◽  
pp. 162
Author(s):  
Dlzar A. Kheder ◽  
Omar A. M. Al-Habib ◽  
Lina N. Adam
Keyword(s):  
Ion Channels ◽  
Signal Transduction Pathway ◽  
Aortic Ring ◽  
Katp Channels ◽  
Inhibitory Effect ◽  
K Channel ◽  
Transduction Pathway ◽  
Aromatic Plants ◽  
Vasodilatory Effect

The monoterpene, α-terpinyle acetate (TA) is a constituent of essential oils present in aromatic plants. Since the role of ion channels and endothelial hyperpolarizing factors in TA induced relaxation in rat’s aorta is unknown, the current study aimed to study the mechanism underlying the vasodilatory effect of TA in isolated aortic rings. Terpinyle acetate induced a potent vasodilation in rat aortic rings with a percentage of relaxation of 63.79 %. The results of the role of K+ channel subtypes in vasorelaxation revealed that both Kv and KATP played a major role since GLIB produced a maximum percent of inhibition in the relaxation produced by TA to 8.91 %; this was followed by 4-AP in which the percent of inhibition reduced to 14.95. On the other hand, Kir played no role in the TA induced vasorelaxation since BaCl2 did not produce any inhibition in aortic relaxation. Furthermore, also L-type Ca2+ channel played no role in TA induced relaxation since the L-type Ca2+ channel inhibitor Nifedipine did not reduce the percent of relaxation. Endothelium also played a considerable role in the induced vasorelaxation since, in denuded aorta, the percent of relaxation was reduced to 36%. Preincubation of the aortic ring with methylene blue, a soluble cGMP inhibitor also significantly reduced the TA induced relaxation to 16.39%. In contrast, preincubation with cyclooxygenase inhibitor Indomethacin did not produce any inhibitory effect on AT induced vasorelaxation. It can be concluded from these novel results that AT induced vasorelaxation involve the activation of KV, KATP channels and at least partly dependent on endothelium via the activation NO-cGMP signal transduction pathway.

scholarly journals Ion Channels in Epithelial Dynamics and Morphogenesis

Cells ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 2280
Author(s):  
Ankit Roy Choudhury ◽  
Jörg Großhans ◽  
Deqing Kong
Keyword(s):  
Nervous System ◽  
Ion Channels ◽  
Epithelial Cells ◽  
Cell Types ◽  
Mechanical Forces ◽  
Morphogenetic Movements ◽  
Mechanosensitive Ion Channels ◽  
Channel Proteins ◽  
Epithelial Tissues

Mechanosensitive ion channels mediate the neuronal sensation of mechanical signals such as sound, touch, and pain. Recent studies point to a function of these channel proteins in cell types and tissues in addition to the nervous system, such as epithelia, where they have been little studied, and their role has remained elusive. Dynamic epithelia are intrinsically exposed to mechanical forces. A response to pull and push is assumed to constitute an essential part of morphogenetic movements of epithelial tissues, for example. Mechano-gated channels may participate in sensing and responding to such forces. In this review, focusing on Drosophila, we highlight recent results that will guide further investigations concerned with the mechanistic role of these ion channels in epithelial cells.

scholarly journals Ion Channels Involved in Substance P-Mediated Nociception and Antinociception

2019 ◽  
Vol 20 (7) ◽  
pp. 1596 ◽  
Author(s):  
Chu-Ting Chang ◽  
Bo-Yang Jiang ◽  
Chih-Cheng Chen
Keyword(s):  
Amino Acid ◽  
Ion Channels ◽  
Substance P ◽  
Drug Development ◽  
Cell Types ◽  
Analgesic Drug ◽  
Differential Cell ◽  
Neurokinin 1

Substance P (SP), an 11-amino-acid neuropeptide, has long been considered an effector of pain. However, accumulating studies have proposed a paradoxical role of SP in anti-nociception. Here, we review studies of SP-mediated nociception and anti-nociception in terms of peptide features, SP-modulated ion channels, and differential effector systems underlying neurokinin 1 receptors (NK1Rs) in differential cell types to elucidate the effect of SP and further our understanding of SP in anti-nociception. Most importantly, understanding the anti-nociceptive SP-NK1R pathway would provide new insights for analgesic drug development.

scholarly journals Laminin-binding integrins and their tetraspanin partners as potential antimetastatic targets

2010 ◽  
Vol 12 ◽  
Author(s):  
Christopher S. Stipp
Keyword(s):  
Plasma Membrane ◽  
Cell Types ◽  
Cell Junctions ◽  
Control Mechanisms ◽  
Membrane Domains ◽  
The Stability ◽  
Different Cell Types ◽  
Integrin Family ◽  
Laminin Binding

Within the integrin family of cell adhesion receptors, integrins α3β1, α6β1, α6β4 and α7β1 make up a laminin-binding subfamily. The literature is divided on the role of these laminin-binding integrins in metastasis, with different studies indicating either pro- or antimetastatic functions. The opposing roles of the laminin-binding integrins in different settings might derive in part from their unusually robust associations with tetraspanin proteins. Tetraspanins organise integrins into multiprotein complexes within discrete plasma membrane domains termed tetraspanin-enriched microdomains (TEMs). TEM association is crucial to the strikingly rapid cell migration mediated by some of the laminin-binding integrins. However, emerging data suggest that laminin-binding integrins also promote the stability of E-cadherin-based cell–cell junctions, and that tetraspanins are essential for this function as well. Thus, TEM association endows the laminin-binding integrins with both pro-invasive functions (rapid migration) and anti-invasive functions (stable cell junctions), and the composition of TEMs in different cell types might help determine the balance between these opposing activities. Unravelling the tetraspanin control mechanisms that regulate laminin-binding integrins will help to define the settings where inhibiting the function of these integrins would be helpful rather than harmful, and may create opportunities to modulate integrin activity in more sophisticated ways than simple functional blockade.

scholarly journals Complex role of STIM1 in the activation of store-independent Orai1/3 channels

2014 ◽  
Vol 143 (3) ◽  
pp. 345-359 ◽  
Author(s):  
Xuexin Zhang ◽  
Wei Zhang ◽  
José C. González-Cobos ◽  
Isaac Jardin ◽  
Christoph Romanin ◽  
...  
Keyword(s):  
Patch Clamp ◽  
Cell Types ◽  
Hek293 Cells ◽  
Patch Clamp Recording ◽  
Channel Activation ◽  
Whole Cell ◽  
Perforated Patch ◽  
Crac Channels ◽  
Crac Channel

Orai proteins contribute to Ca2+ entry into cells through both store-dependent, Ca2+ release–activated Ca2+ (CRAC) channels (Orai1) and store-independent, arachidonic acid (AA)-regulated Ca2+ (ARC) and leukotriene C4 (LTC4)-regulated Ca2+ (LRC) channels (Orai1/3 heteromultimers). Although activated by fundamentally different mechanisms, CRAC channels, like ARC and LRC channels, require stromal interacting molecule 1 (STIM1). The role of endoplasmic reticulum–resident STIM1 (ER-STIM1) in CRAC channel activation is widely accepted. Although ER-STIM1 is necessary and sufficient for LRC channel activation in vascular smooth muscle cells (VSMCs), the minor pool of STIM1 located at the plasma membrane (PM-STIM1) is necessary for ARC channel activation in HEK293 cells. To determine whether ARC and LRC conductances are mediated by the same or different populations of STIM1, Orai1, and Orai3 proteins, we used whole-cell and perforated patch-clamp recording to compare AA- and LTC4-activated currents in VSMCs and HEK293 cells. We found that both cell types show indistinguishable nonadditive LTC4- and AA-activated currents that require both Orai1 and Orai3, suggesting that both conductances are mediated by the same channel. Experiments using a nonmetabolizable form of AA or an inhibitor of 5-lipooxygenase suggested that ARC and LRC currents in both cell types could be activated by either LTC4 or AA, with LTC4 being more potent. Although PM-STIM1 was required for current activation by LTC4 and AA under whole-cell patch-clamp recordings in both cell types, ER-STIM1 was sufficient with perforated patch recordings. These results demonstrate that ARC and LRC currents are mediated by the same cellular populations of STIM1, Orai1, and Orai3, and suggest a complex role for both ER-STIM1 and PM-STIM1 in regulating these store-independent Orai1/3 channels.

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