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Biochimica Et Biophysica Acta.... Jan 2018This review focuses on the biophysical properties and structure of the pore and vestibule of homotypic gap junction channels as they relate to channel permeability and... (Review)
Review
This review focuses on the biophysical properties and structure of the pore and vestibule of homotypic gap junction channels as they relate to channel permeability and selectivity. Gap junction channels are unique in their sole role to connect the cytoplasm of two adjacent cells. In general, these channels are considered to be poorly selective, possess open probabilities approximating unity, and exhibit mean open times ranging from milliseconds to seconds. These properties suggest that such channels can function as delivery pathways from cell to cell for solutes that are significantly larger than monovalent ions. We have taken quantitative data from published works concerning unitary conductance, ion flux, and permeability for homotypic connexin 43 (Cx43), Cx40, Cx26, Cx50, and Cx37, and performed a comparative analysis of conductance and/or ion/solute flux versus diffusion coefficient. The analysis of monovalent cation flux portrays the pore as equivalent to an aqueous space where hydrogen bonding and weak interactions with binding sites dominate. For larger solutes, size, shape and charge are also significant components in determining the permeation rate. This article is part of a Special Issue entitled: Gap Junction Proteins edited by Jean Claude Herve.
Topics: Animals; Cell Membrane Permeability; Connexins; Gap Junctions; Humans; Ion Channels; Ion Transport
PubMed: 28690048
DOI: 10.1016/j.bbamem.2017.07.002 -
Cells Oct 2023Epithelial transport is a multifaceted process crucial for maintaining normal physiological functions in the human body. This comprehensive review delves into the... (Review)
Review
Epithelial transport is a multifaceted process crucial for maintaining normal physiological functions in the human body. This comprehensive review delves into the pathophysiological mechanisms underlying epithelial transport and its significance in disease pathogenesis. Beginning with an introduction to epithelial transport, it covers various forms, including ion, water, and nutrient transfer, followed by an exploration of the processes governing ion transport and hormonal regulation. The review then addresses genetic disorders, like cystic fibrosis and Bartter syndrome, that affect epithelial transport. Furthermore, it investigates the involvement of epithelial transport in the pathophysiology of conditions such as diarrhea, hypertension, and edema. Finally, the review analyzes the impact of renal disease on epithelial transport and highlights the potential for future research to uncover novel therapeutic interventions for conditions like cystic fibrosis, hypertension, and renal failure.
Topics: Humans; Cystic Fibrosis; Cystic Fibrosis Transmembrane Conductance Regulator; Epithelial Cells; Ion Transport; Hypertension
PubMed: 37887299
DOI: 10.3390/cells12202455 -
Nature Communications Aug 2023The hinged-lid model was long accepted as the canonical model for fast inactivation in Nav channels. It predicts that the hydrophobic IFM motif acts intracellularly as...
The hinged-lid model was long accepted as the canonical model for fast inactivation in Nav channels. It predicts that the hydrophobic IFM motif acts intracellularly as the gating particle that binds and occludes the pore during fast inactivation. However, the observation in recent high-resolution structures that the bound IFM motif is located far from the pore, contradicts this preconception. Here, we provide a mechanistic reinterpretation of fast inactivation based on structural analysis and ionic/gating current measurements. We demonstrate that in Nav1.4 the final inactivation gate is comprised of two hydrophobic rings at the bottom of S6 helices. These rings function in series and close downstream of IFM binding. Reducing the volume of the sidechain in both rings leads to a partially conductive, leaky inactivated state and decreases the selectivity for Na ion. Altogether, we present an alternative molecular framework to describe fast inactivation.
Topics: Ear Auricle; Electric Conductivity; Ion Transport; Ions
PubMed: 37604801
DOI: 10.1038/s41467-023-40514-4 -
Cell Calcium Jan 2018
Topics: Animals; Calcium; Calcium Signaling; Cell Death; Cell Survival; Humans; Ion Transport; Voltage-Dependent Anion Channel 1
PubMed: 28965649
DOI: 10.1016/j.ceca.2017.09.001 -
International Journal of Laboratory... May 2018Hydration status is critical for erythrocyte survival and is mainly determined by intracellular cation content. Active pumps, passive transporters, and ion channels are... (Review)
Review
Hydration status is critical for erythrocyte survival and is mainly determined by intracellular cation content. Active pumps, passive transporters, and ion channels are the key components of volume homeostasis, whereas water passively fits ionic movements. Whenever cation content increases, erythrocyte swells, whereas it shrinks when cation content decreases. Thus, inappropriate cation leak causes erythrocyte hydration disorders, hemolytic anemia, and characteristic red cell shape abnormalities named stomatocytosis. All types of stomatocytosis either overhydrated or dehydrated are linked to inherited or de novo mutations in genes encoding ion transporters or channels. Although intracellular ion content can be assessed by experimental methods, laboratory diagnosis is guided by a combination of red blood cell parameters and deformability measurement when possible, and confirmed by sequencing of the putative genes. A better knowledge of the mechanisms underlying erythrocyte hydration imbalance will further lead to therapeutic improvements.
Topics: Anemia, Hemolytic; Erythrocyte Volume; Humans; Ion Transport; Water-Electrolyte Imbalance
PubMed: 29741259
DOI: 10.1111/ijlh.12820 -
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 -
Current Topics in Membranes 2018Ion Transport across the cell membrane is required to maintain cell volume homeostasis. In response to changes in extracellular osmolarity, most cells activate specific... (Review)
Review
Ion Transport across the cell membrane is required to maintain cell volume homeostasis. In response to changes in extracellular osmolarity, most cells activate specific metabolic or membrane-transport pathways to respond to cell swelling or shrinkage and return their volume to its normal resting state. This process involves the rapid adjustment of the activities of channels and transporters that mediate flux of K, Na, Cl, and small organic osmolytes. Cation chloride cotransporters (CCCs) NKCCs and KCCs are a family of membrane proteins modulated by changes in cell volume and/or in the intracellular chloride concentration ([Cl]). Cell swelling triggers regulatory volume decrease (RVD), promoting solute and water efflux to restore normal cell volume. Swelling-activated KCCs mediate RVD in most cell types. In contrast, cell shrinkage triggers regulatory volume increase (RVI), which involves the activation of the NKCC1 cotransporter of the CCC family. Regulation of the CCCs during RVI and RVD by protein phosphorylation is a well-characterized mechanism, where WNK kinases and their downstream kinase substrates, SPAK and OSR1 constitute the essential phospho-regulators. WNKs-SPAK/OSR1-CCCs complex is required to regulate cell shrinkage-induced RVI or cell swelling-induced RVD via activating or inhibitory phosphorylation of NKCCs or KCCs, respectively. WNK1 and WNK4 kinases have been established as [Cl] sensors/regulators, while a role for WNK3 kinase as a cell volume-sensing kinase has emerged and is proposed in this chapter.
Topics: Animals; Cell Size; Chlorides; Humans; Ion Transport; Phosphorylation; Sodium; Sodium-Potassium-Chloride Symporters
PubMed: 30243433
DOI: 10.1016/bs.ctm.2018.08.002 -
Chemistry (Weinheim An Der Bergstrasse,... May 2021Anion receptors can be used to transport ions across lipid bilayers, which has potential for therapeutic applications. Synthetic bicarbonate transporters are of...
Anion receptors can be used to transport ions across lipid bilayers, which has potential for therapeutic applications. Synthetic bicarbonate transporters are of particular interest, as defects in transmembrane transport of bicarbonate are associated with various diseases. However, no convenient method exists to directly observe bicarbonate transport and study the mechanisms involved. Here, an assay is presented that allows the kinetics of bicarbonate transport into liposomes to be monitored directly and with great sensitivity. The assay utilises an encapsulated europium(III) complex, which exhibits a large increase in emission intensity upon binding bicarbonate. Mechanisms involving CO diffusion and the dissipation of a pH gradient are shown to be able to lead to an increase in bicarbonate concentration within liposomes, without transport of the anion occurring at all. By distinguishing these alternative mechanisms from actual bicarbonate transport, this assay will inform the future development of bicarbonate transporters.
Topics: Bicarbonates; Biological Transport; Hydrogen-Ion Concentration; Ion Transport; Kinetics; Lipid Bilayers
PubMed: 33932059
DOI: 10.1002/chem.202100491 -
The Journal of General Physiology Oct 2016Ion channels are membrane proteins that mediate efficient ion transport across the hydrophobic core of cell membranes, an unlikely process in their absence. K(+)... (Review)
Review
Ion channels are membrane proteins that mediate efficient ion transport across the hydrophobic core of cell membranes, an unlikely process in their absence. K(+) channels discriminate K(+) over cations with similar radii with extraordinary selectivity and display a wide diversity of ion transport rates, covering differences of two orders of magnitude in unitary conductance. The pore domains of large- and small-conductance K(+) channels share a general architectural design comprising a conserved narrow selectivity filter, which forms intimate interactions with permeant ions, flanked by two wider vestibules toward the internal and external openings. In large-conductance K(+) channels, the inner vestibule is wide, whereas in small-conductance channels it is narrow. Here we raise the idea that the physical dimensions of the hydrophobic internal vestibule limit ion transport in K(+) channels, accounting for their diversity in unitary conductance.
Topics: Ion Transport; Models, Molecular; Potassium; Potassium Channels; Protein Conformation
PubMed: 27619418
DOI: 10.1085/jgp.201611625 -
Biochemistry. Biokhimiia Sep 2016Optogenetics technology (using light-sensitive microbial proteins to control animal cell physiology) is becoming increasingly popular in laboratories around the world.... (Review)
Review
Optogenetics technology (using light-sensitive microbial proteins to control animal cell physiology) is becoming increasingly popular in laboratories around the world. Among these proteins, particularly important are rhodopsins that transport ions across the membrane and are used in optogenetics to regulate membrane potential by light, mostly in neurons. Although rhodopsin ion pumps transport only one charge per captured photon, channelrhodopsins are capable of more efficient passive transport. In this review, we follow the history of channelrhodopsin discovery in flagellate algae and discuss the latest addition to the channelrhodopsin family, channels with anion, rather than cation, selectivity.
Topics: Cell Membrane; Ion Transport; Light; Membrane Potentials; Optogenetics; Rhodopsins, Microbial
PubMed: 27682165
DOI: 10.1134/S0006297916090029