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Journal of the American Chemical Society Jun 2022Ion transport across lipid membranes in biology is controlled by stimuli-responsive membrane channels and molecular machine ion pumps such as ATPases. Here, we report a...
Ion transport across lipid membranes in biology is controlled by stimuli-responsive membrane channels and molecular machine ion pumps such as ATPases. Here, we report a synthetic molecular machine-like ion transport relay, in which transporters on opposite sides of a lipid bilayer membrane facilitate transport by passing ions between them. By incorporating a photo-responsive telescopic arm into the relay design, this process is reversibly controlled in response to irradiation with blue and green light. Transport occurs only in the extended state when the length of the arm is sufficient to pass the anion between transporters located on opposite sides of the membrane. In contrast, the contracted state of the telescopic arm is too short to mediate effective transport. The system acts as a stimuli-responsive ensemble of machine-like components, reminiscent of robotic arms in a factory assembly line, working cooperatively to mediate ion transport. This work points to new prospects for using lipid bilayer membranes as scaffolds for confining, orientating, and controlling the relative positions of molecular machines, thus enabling multiple components to work in concert and opening up new applications in biological contexts.
Topics: Anions; Biological Transport; Ion Channels; Ion Transport; Lipid Bilayers
PubMed: 35652660
DOI: 10.1021/jacs.2c02612 -
Philosophical Transactions of the Royal... Mar 2014Ion transport across the cell membrane mediated by channels and carriers participate in the regulation of tumour cell survival, death and motility. Moreover, the altered... (Review)
Review
Ion transport across the cell membrane mediated by channels and carriers participate in the regulation of tumour cell survival, death and motility. Moreover, the altered regulation of channels and carriers is part of neoplastic transformation. Experimental modification of channel and transporter activity impacts tumour cell survival, proliferation, malignant progression, invasive behaviour or therapy resistance of tumour cells. A wide variety of distinct Ca(2+) permeable channels, K(+) channels, Na(+) channels and anion channels have been implicated in tumour growth and metastasis. Further experimental information is, however, needed to define the specific role of individual channel isoforms critically important for malignancy. Compelling experimental evidence supports the assumption that the pharmacological inhibition of ion channels or their regulators may be attractive targets to counteract tumour growth, prevent metastasis and overcome therapy resistance of tumour cells. This short review discusses the role of Ca(2+) permeable channels, K(+) channels, Na(+) channels and anion channels in tumour growth and metastasis and the therapeutic potential of respective inhibitors.
Topics: Drug Delivery Systems; Humans; Ion Channels; Ion Transport; Models, Biological; Neoplasm Metastasis; Neoplasms
PubMed: 24493756
DOI: 10.1098/rstb.2013.0108 -
ChemPlusChem Nov 2022The development of synthetic anion transporters is motivated by their potential application as treatment for diseases that originate from deficient anion transport by... (Review)
Review
The development of synthetic anion transporters is motivated by their potential application as treatment for diseases that originate from deficient anion transport by natural proteins. Transport of bicarbonate is important for crucial biological functions such as respiration and digestion. Despite this biological relevance, bicarbonate transport has not been as widely studied as chloride transport. Herein we present an overview of the synthetic receptors that have been studied as bicarbonate transporters, together with the different assays used to perform transport studies in large unilamellar vesicles. We highlight the most active transporters and comment on the nature of the functional groups present in active and inactive compounds. We also address recent mechanistic studies that have revealed different processes that can lead to net transport of bicarbonate, as well as studies reported in cells and tissues, and comment on the key challenges for the further development of bicarbonate transporters.
Topics: Bicarbonates; Biological Transport; Ion Transport
PubMed: 36414387
DOI: 10.1002/cplu.202200266 -
Progress in Retinal and Eye Research Jan 2012Epithelia of the cornea, lens and retina contain a vast array of ion channels and pumps. Together they produce a polarized flow of ions in and out of cells, as well as... (Review)
Review
Epithelia of the cornea, lens and retina contain a vast array of ion channels and pumps. Together they produce a polarized flow of ions in and out of cells, as well as across the epithelia. These naturally occurring ion fluxes are essential to the hydration and metabolism of the ocular tissues, especially for the avascular cornea and lens. The directional transport of ions generates electric fields and currents in those tissues. Applied electric fields affect migration, division and proliferation of ocular cells which are important in homeostasis and healing of the ocular tissues. Abnormalities in any of those aspects may underlie many ocular diseases, for example chronic corneal ulcers, posterior capsule opacity after cataract surgery, and retinopathies. Electric field-inducing cellular responses, termed electrical signaling here, therefore may be an unexpected yet powerful mechanism in regulating ocular cell behavior. Both endogenous electric fields and applied electric fields could be exploited to regulate ocular cells. We aim to briefly describe the physiology of the naturally occurring electrical activities in the corneal, lens, and retinal epithelia, to provide experimental evidence of the effects of electric fields on ocular cell behaviors, and to suggest possible clinical implications.
Topics: Animals; Cell Movement; Cell Proliferation; Cornea; Electric Stimulation; Electrophysiological Phenomena; Humans; Ion Transport; Lens, Crystalline; Mice; Retinal Pigment Epithelium; Wound Healing
PubMed: 22020127
DOI: 10.1016/j.preteyeres.2011.10.001 -
ELife Aug 2020In order to enter a cell, an ammonium ion must first dissociate to form an ammonia molecule and a hydrogen ion (a proton), which then pass through the cell membrane...
In order to enter a cell, an ammonium ion must first dissociate to form an ammonia molecule and a hydrogen ion (a proton), which then pass through the cell membrane separately and recombine inside.
Topics: Ammonia; Ammonium Compounds; Ion Transport; Nitrosomonas; Oxidation-Reduction
PubMed: 32840481
DOI: 10.7554/eLife.61148 -
Physiological Reviews Jan 2019The thick ascending limb plays a key role in maintaining water and electrolyte balance. The importance of this segment in regulating blood pressure is evidenced by the... (Review)
Review
The thick ascending limb plays a key role in maintaining water and electrolyte balance. The importance of this segment in regulating blood pressure is evidenced by the effect of loop diuretics or local genetic defects on this parameter. Hormones and factors produced by thick ascending limbs have both autocrine and paracrine effects, which can extend prohypertensive signaling to other structures of the nephron. In this review, we discuss the role of the thick ascending limb in the development of hypertension, not as a sole participant, but one that works within the rich biological context of the renal medulla. We first provide an overview of the basic physiology of the segment and the anatomical considerations necessary to understand its relationship with other renal structures. We explore the physiopathological changes in thick ascending limbs occurring in both genetic and induced animal models of hypertension. We then discuss the racial differences and genetic defects that affect blood pressure in humans through changes in thick ascending limb transport rates. Throughout the text, we scrutinize methodologies and discuss the limitations of research techniques that, when overlooked, can lead investigators to make erroneous conclusions. Thus, in addition to advancing an understanding of the basic mechanisms of physiology, the ultimate goal of this work is to understand our research tools, to make better use of them, and to contextualize research data. Future advances in renal hypertension research will require not only collection of new experimental data, but also integration of our current knowledge.
Topics: Animals; Blood Pressure; Extremities; Humans; Hypertension; Ion Transport; Sodium; Water-Electrolyte Balance
PubMed: 30354966
DOI: 10.1152/physrev.00055.2017 -
Current Opinion in Gastroenterology Mar 2009In recent years, the field of intestinal physiology has witnessed significant progress in our understanding of the expression and function of ion transport proteins and... (Review)
Review
PURPOSE OF REVIEW
In recent years, the field of intestinal physiology has witnessed significant progress in our understanding of the expression and function of ion transport proteins and their genes under physiological and pathophysiological conditions. This review will present some of these most recent advances in the small intestinal ion transport mechanisms.
RECENT FINDINGS
One of the new and exciting aspects of this field has been the integration of function and structure of several intestinal transport processes. This is well exemplified by the discussed intricacies of intestinal bicarbonate secretion as well as the role of scaffolding PDZ proteins interacting with several transporters. We also discuss some of the most recent data pointing to the role of ion transporters in the pathogenesis of inflammation-associated diarrhea and their potential role in the maintenance of epithelial integrity.
SUMMARY
Mouse models deficient in some of the key genes encoding ion transporters and their adapter proteins continue to provide important clues into intestinal transport processes. Several of the new in-vivo findings revise or complement past paradigms, many of which were derived from in-vitro approaches. New data on the interdependent functions of multiple transporters, as exemplified here by intestinal bicarbonate secretion, increase the complexity of the intestinal ion transport mechanisms and continue to contribute to a more integrated view of the transport phenomena in the gut. Data from patients and mouse models of intestinal inflammation also increase our understanding of the pathophysiology of inflammation-associated diarrhea.
Topics: Animals; Bicarbonates; Duodenum; Humans; Inflammation; Intestinal Mucosa; Ion Transport; Membrane Transport Proteins; Mice; Models, Animal; Phosphoproteins; Sodium-Hydrogen Exchangers
PubMed: 19528875
DOI: 10.1097/MOG.0b013e3283260900 -
The Journal of General Physiology Jul 2015The crystal structures of channels and transporters reveal the chemical nature of ion-binding sites and, thereby, constrain mechanistic models for their transport... (Review)
Review
The crystal structures of channels and transporters reveal the chemical nature of ion-binding sites and, thereby, constrain mechanistic models for their transport processes. However, these structures, in and of themselves, do not reveal equilibrium selectivity or transport preferences, which can be discerned only from various functional assays. In this Review, I explore the relationship between cation transport protein structures, equilibrium binding measurements, and ion transport selectivity. The primary focus is on K(+)-selective channels and nonselective cation channels because they have been extensively studied both functionally and structurally, but the principles discussed are relevant to other transport proteins and molecules.
Topics: Binding Sites; Cations; Crystallography, X-Ray; Ion Channel Gating; Ion Transport; Kinetics; Potassium Channels
PubMed: 26078056
DOI: 10.1085/jgp.201511371 -
Microcirculation (New York, N.Y. : 1994) Jul 2012Movement of ions (Ca(2+) , K(+) , Na(+) , and Cl(-) ) and second messenger molecules like inositol 1, 4, 5-trisphosphate inside and in between different cells is the... (Review)
Review
Movement of ions (Ca(2+) , K(+) , Na(+) , and Cl(-) ) and second messenger molecules like inositol 1, 4, 5-trisphosphate inside and in between different cells is the basis of many signaling mechanisms in the microcirculation. In spite of the vast experimental efforts directed toward evaluation of these fluxes, it has been a challenge to establish their roles in many essential microcirculatory phenomena. Recently, detailed theoretical models of calcium dynamics and plasma membrane electrophysiology have emerged to assist in the quantification of these intra and intercellular fluxes and enhance understanding of their physiological importance. This perspective reviews selected models relevant to estimation of such intra and intercellular ionic and second messenger fluxes and prediction of their relative significance to a variety of vascular phenomena, such as myoendothelial feedback, conducted responses, and vasomotion.
Topics: Animals; Cell Communication; Endothelium, Vascular; Hemodynamics; Humans; Ion Transport; Ions; Models, Cardiovascular; Muscle, Smooth, Vascular; Second Messenger Systems
PubMed: 22340204
DOI: 10.1111/j.1549-8719.2012.00171.x -
Philosophical Transactions of the Royal... Mar 2014Cell migration is a central component of the metastatic cascade requiring a concerted action of ion channels and transporters (migration-associated transportome),... (Review)
Review
Cell migration is a central component of the metastatic cascade requiring a concerted action of ion channels and transporters (migration-associated transportome), cytoskeletal elements and signalling cascades. Ion transport proteins and aquaporins contribute to tumour cell migration and invasion among other things by inducing local volume changes and/or by modulating Ca(2+) and H(+) signalling. Targeting cell migration therapeutically bears great clinical potential, because it is a prerequisite for metastasis. Ion transport proteins appear to be attractive candidate target proteins for this purpose because they are easily accessible as membrane proteins and often overexpressed or activated in cancer. Importantly, a number of clinically widely used drugs are available whose anticipated efficacy as anti-tumour drugs, however, has now only begun to be evaluated.
Topics: Cell Movement; Humans; Ion Channels; Ion Transport; Models, Biological; Neoplasm Invasiveness; Neoplasm Metastasis; Neoplasms
PubMed: 24493750
DOI: 10.1098/rstb.2013.0102