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Seminars in Nephrology Jul 2019The epithelium of the kidney collecting duct (CD) is composed mainly of two different types of cells with distinct and complementary functions. CD principal cells... (Review)
Review
The epithelium of the kidney collecting duct (CD) is composed mainly of two different types of cells with distinct and complementary functions. CD principal cells traditionally have been considered to have a major role in Na and water regulation, while intercalated cells (ICs) were thought to largely modulate acid-base homeostasis. In recent years, our understanding of IC function has improved significantly owing to new research findings. Thus, we now have a new model for CD transport that integrates mechanisms of salt and water reabsorption, K homeostasis, and acid-base status between principal cells and ICs. There are three main types of ICs (type A, type B, and non-A, non-B), which first appear in the late distal convoluted tubule or in the connecting segment in a species-dependent manner. ICs can be detected in CD from cortex to the initial part of the inner medulla, although some transport proteins that are key components of ICs also are present in medullary CD, cells considered inner medullary. Of the three types of ICs, each has a distinct morphology and expresses different complements of membrane transport proteins that translate into very different functions in homeostasis and contributions to CD luminal pro-urine composition. This review includes recent discoveries in IC intracellular and paracrine signaling that contributes to acid-base regulation as well as Na, Cl, K, and Ca homeostasis. Thus, these new findings highlight the potential role of ICs as targets for potential hypertension treatments.
Topics: Acid-Base Equilibrium; Animals; Calcium Channels; Chloride Channels; Epithelial Cells; Humans; Hydrogen-Ion Concentration; Ion Transport; Kidney Tubules, Collecting; Potassium Channels; Sodium Channels
PubMed: 31300091
DOI: 10.1016/j.semnephrol.2019.04.005 -
Sheng Li Xue Bao : [Acta Physiologica... Jun 2016Ion channels and transporters represent two major types of pathways of transmembrane transport for ions. Distinct from ion channels which conduct passive ionic... (Review)
Review
Ion channels and transporters represent two major types of pathways of transmembrane transport for ions. Distinct from ion channels which conduct passive ionic diffusion, ion transporters mediate active transport of ions. In the perspective of biochemistry, ion transporters are enzymes that catalyze the movement of ions across the plasma membrane. In the present review, we selected the Na(+)/HCO3(-) cotransporter (NBC) as an example to analyze the key biochemical and biophysical properties of ion transporters, including stoichiometry, turnover number and transport capacity. Moreover, we provided an analysis of the electrophysiological principles of NBC based on the laws of thermodynamics. Based on the thermodynamical analysis, we showed how the stoichiometry of an NBC determines the direction of its ion transport. Finally, we reviewed the methodology for experimental determination of the stoichiometry of NBC, as well as the physiological significance of the stoichiometry of NBCs in specific tissues.
Topics: Electrophysiological Phenomena; Ion Transport; Sodium-Bicarbonate Symporters
PubMed: 27350205
DOI: No ID Found -
Biochimica Et Biophysica Acta.... Dec 2020TRPC6 channel is widely expressed in most human tissues and participates in a number of physiological processes. TRPC6 belongs to the DAG-activated subfamily of... (Review)
Review
TRPC6 channel is widely expressed in most human tissues and participates in a number of physiological processes. TRPC6 belongs to the DAG-activated subfamily of channels, but has also been postulated as a mediator in the store-operated calcium entry pathway. The recent characterization of TRPC6 crystal structure has granted a wonderful tool to finally dissect and understand TRPC6 physiological and biophysical properties. Growing evidences have demonstrated that the pattern of expression of TRPC6 proteins is upregulated in several pathophysiological conditions, including breast cancer. However, the real role of TRPC6 in breast cancer persists still unknown. Here we present the current state of the art concerning the function and significance of TRPC6 in this disease. Future investigations should be focus in the creation and identification of compounds that specifically target the channel to ameliorate TRPC6-related diseases.
Topics: Breast Neoplasms; Calcium; Female; Gene Expression Regulation, Neoplastic; Humans; Ion Transport; TRPC6 Cation Channel
PubMed: 32822726
DOI: 10.1016/j.bbamcr.2020.118828 -
Clinical Journal of the American... Nov 2014The thick ascending limb occupies a central anatomic and functional position in human renal physiology, with critical roles in the defense of the extracellular fluid... (Review)
Review
The thick ascending limb occupies a central anatomic and functional position in human renal physiology, with critical roles in the defense of the extracellular fluid volume, the urinary concentrating mechanism, calcium and magnesium homeostasis, bicarbonate and ammonium homeostasis, and urinary protein composition. The last decade has witnessed tremendous progress in the understanding of the molecular physiology and pathophysiology of this nephron segment. These advances are the subject of this review, with emphasis on particularly recent developments.
Topics: Ammonium Compounds; Bicarbonates; Calcium; Chlorides; Homeostasis; Humans; Ion Transport; Loop of Henle; Magnesium; Potassium; Sodium; Uromodulin
PubMed: 25318757
DOI: 10.2215/CJN.04480413 -
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 -
International Journal of Molecular... Jan 2024This Special Issue focuses on the significance of ion-transporting proteins, such as ion channels and transporters, providing evidence for their significant contribution...
This Special Issue focuses on the significance of ion-transporting proteins, such as ion channels and transporters, providing evidence for their significant contribution to bodily and cellular functions via the regulation of signal transduction and ionic environments [...].
Topics: Humans; Ion Channels; Ion Transport; Signal Transduction
PubMed: 38339004
DOI: 10.3390/ijms25031726 -
American Journal of Respiratory Cell... Oct 2023
Topics: Humans; Glutamine; Pulmonary Fibrosis; Biological Transport; Ion Transport; Minor Histocompatibility Antigens; Amino Acid Transport System ASC
PubMed: 37463521
DOI: 10.1165/rcmb.2023-0189ED -
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 -
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 -
Expert Opinion on Therapeutic Targets Aug 2017The mammalian SPS1-related proline/alanine-rich serine-threonine kinase SPAK (STK39) modulates ion transport across and between epithelial cells in response to... (Review)
Review
The mammalian SPS1-related proline/alanine-rich serine-threonine kinase SPAK (STK39) modulates ion transport across and between epithelial cells in response to environmental stimuli such osmotic stress and inflammation. Research over the last decade has established a central role for SPAK in the regulation of ion and water transport in the distal nephron, colonic crypts, and pancreatic ducts, and has implicated deregulated SPAK signaling in NaCl-sensitive hypertension, ulcerative colitis and Crohn's disease, and cystic fibrosis. Areas covered: We review recent advances in our understanding of the role of SPAK kinase in the regulation of epithelial transport. We highlight how SPAK signaling - including its upstream Cl sensitive activators, the WNK kinases, and its downstream ion transport targets, the cation- Cl cotransporters contribute to human disease. We discuss prospects for the pharmacotherapeutic targeting of SPAK kinase in specific human disorders that feature impaired epithelial homeostasis. Expert opinion: The development of novel drugs that antagonize the SPAK-WNK interaction, inhibit SPAK kinase activity, or disrupt SPAK kinase activation by interfering with its binding to MO25α/β could be useful adjuncts in essential hypertension, inflammatory colitis, and cystic fibrosis.
Topics: Animals; Colitis; Cystic Fibrosis; Drug Design; Epithelial Cells; Essential Hypertension; Humans; Hypertension; Ion Transport; Molecular Targeted Therapy; Protein Serine-Threonine Kinases; Signal Transduction
PubMed: 28679296
DOI: 10.1080/14728222.2017.1351949