On the relationship between anion binding and chloride conductance in the CFTR anion channel

Handbooks of physiology state that the strategy adopted by red blood cells (RBCs) to preserve cell volume is to maintain membrane permeability for cations at its minimum. However, enhanced cation permeability can be measured and observed in specific physiological and pathophysiological situations such as in vivo senescence, storage at low temperature, sickle cell anemia and many other genetic defects affecting transporters, membrane or cytoskeletal proteins. Among cation pathways, cation channels are able to dissipate rapidly the gradients that are built and maintained by the sodium and calcium pumps. These situations are very well-documented but a mechanistic understanding of complex electrophysiological events underlying ion transports is still lacking. In addition, non-selective cation (NSC) channels present in the RBC membrane have proven difficult to molecular identification and functional characterization. For instance, NSC channel activity can be elicited by Low Ionic Strength conditions (LIS): the associated change in membrane potential triggers its opening in a voltage dependent manner. But, whereas this depolarizing media produces a spectacular activation of NSC channel, Gárdos channel-evoked hyperpolarization's have been shown to induce sodium entry through a pathway thought to be conductive and termed Pcat. Using the CCCP method, which allows to follow fast changes in membrane potential, we show here (i) that hyperpolarization elicited by Gárdos channel activation triggers sodium entry through a conductive pathway, (ii) that chloride conductance inhibition unveils such conductive cationic conductance, (iii) that the use of the specific chloride conductance inhibitor NS3623 (a derivative of Neurosearch compound NS1652), at concentrations above what is needed for full anion channel block, potentiates the non-selective cation conductance. These results indicate that a non-selective cation channel is likely activated by the changes in the driving force for cations rather than a voltage dependence mechanism per se.

Download Full-text

Synthesis, characterization, photophysics, and anion binding properties of platinum(ii) acetylide complexes with urea group

Dalton Transactions ◽

10.1039/c5dt00307e ◽

2015 ◽

Vol 44 (17) ◽

pp. 7785-7796 ◽

Cited By ~ 10

Author(s):

Zhi-Hui Zhang ◽

Jiewei Liu ◽

Li-Qi Wan ◽

Fang-Ru Jiang ◽

Chi-Keung Lam ◽

...

Keyword(s):

Anion Binding ◽

Binding Properties ◽

Binding Ability ◽

Urea Group ◽

The Relationship

The relationship between the structure and anion-binding ability of platinum(ii) acetylide complexes with urea group has been studied.

Download Full-text

Cryo-EM structures and functional characterization of the lipid scramblase TMEM16F

10.1101/455261 ◽

2018 ◽

Cited By ~ 4

Author(s):

Carolina Alvadia ◽

Novandy K. Lim ◽

Vanessa Clerico Mosina ◽

Gert T. Oostergetel ◽

Raimund Dutzler ◽

...

Keyword(s):

Conformational Changes ◽

Functional Data ◽

Functional Characterization ◽

Anion Channel ◽

Bound State ◽

Striking Similarity ◽

Common Mechanism ◽

Protein Conformations ◽

The Relationship

SUMMARYThe lipid scramblase TMEM16F initiates blood coagulation by catalyzing the exposure of phosphatidylserine in platelets. The protein is part of a family of membrane proteins, which encompasses calcium-activated channels for ions and lipids. Here, we reveal features of TMEM16F that underlie its function as lipid scramblase and ion channel. The cryo-EM structures of TMEM16F in Ca2+-bound and Ca2+-free states display a striking similarity to the scrambling-incompetent anion channel TMEM16A, yet with distinct differences in the catalytic site and in the conformational changes upon activation. In conjunction with functional data, we demonstrate the relationship between ion conduction and lipid scrambling. Although activated by a common mechanism, which likely resembles an equivalent process defined in the homologue nhTMEM16, both functions appear to be mediated by alternate protein conformations, which are at equilibrium in the ligand-bound state.

Download Full-text

A simulation of action potentials in synaptic boutons during presynaptic inhibition

Journal of Neurophysiology ◽

10.1152/jn.1994.71.2.538 ◽

1994 ◽

Vol 71 (2) ◽

pp. 538-549 ◽

Cited By ~ 76

Author(s):

B. Graham ◽

S. Redman

Keyword(s):

Action Potential ◽

Transmitter Release ◽

Action Potentials ◽

Presynaptic Inhibition ◽

Chloride Conductance ◽

Membrane Properties ◽

Published Data ◽

Myelinated Nerve ◽

Synaptic Boutons ◽

The Relationship

1. During presynaptic inhibition, an increased conductance in the membrane of the presynaptic bouton is presumed to reduce the action potential, thereby reducing transmitter release. The object of the simulation has been to determine the magnitude of a chloride conductance required to reduce transmitter release, for various diameters of synaptic boutons, connected to axons with diameters in the range 0.1-1.0 microns. 2. A propagating action potential was simulated in axons connected to either side of a hemispherical bouton. The axons could be myelinated or unmyelinated, while the bouton membrane could be passive, a node of the myelinated nerve, or have the same active properties as the attached unmyelinated nerve. Membrane properties of the axons were derived from mammalian data and scaled to 37 degrees C. 3. A steady-state chloride conductance was included in the bouton membrane, with ECl = -40 mV. The amplitude of the action potential in the bouton was calculated for different diameters of axon and bouton and for different magnitudes of chloride conductance. 4. Using published data on the relationship between the amplitude of a presynaptic action potential and the resulting postsynaptic potential, the relationship between the chloride conductance and the postsynaptic response was calculated for different geometries. Transmitter release was reduced when an action potential was 90 mV or smaller, with no transmission for action potentials smaller than 50 mV. 5. Conductance increases in the range 3 to 10 nS were required to reduce the action potential to 90 mV, depending on the diameter of the axon (0.5-1.0 microns), diameter of the bouton (3-6 microns), whether the bouton had passive or active membrane, and whether the axon was myelinated or unmyelinated. A 3 microns passive bouton connected to a 0.5 micron myelinated axon was most sensitive to the effects of a chloride conductance, while a 6 microns active bouton connected to a 1 micron myelinated nerve was least sensitive to the effects of a chloride conductance. 6. The reduction in the action potential was compared when ECl = -40 mV and when ECl = E(rest) = -80 mV. Inactivation of the sodium conductance by terminal depolarization was the dominant influence on the amplitude of the action potential. 7. Conductances that were sufficient to completely block synaptic transmission at a bouton were insufficient to prevent the spread of the action potential away from that bouton.(ABSTRACT TRUNCATED AT 400 WORDS)

Download Full-text

On the relationship between the mitochondrial inner membrane anion channel and the adenine nucleotide translocase.

Journal of Biological Chemistry ◽

10.1016/s0021-9258(17)34104-2 ◽

1994 ◽

Vol 269 (14) ◽

pp. 10614-10620

Author(s):

M.F. Powers ◽

L.L. Smith ◽

A.D. Beavis

Keyword(s):

Adenine Nucleotide ◽

Anion Channel ◽

Adenine Nucleotide Translocase ◽

Inner Membrane ◽

Mitochondrial Inner Membrane ◽

Inner Membrane Anion Channel ◽

The Relationship

Download Full-text

Cryo-EM structures and functional characterization of the murine lipid scramblase TMEM16F

eLife ◽

10.7554/elife.44365 ◽

2019 ◽

Vol 8 ◽

Cited By ~ 32

Author(s):

Carolina Alvadia ◽

Novandy K Lim ◽

Vanessa Clerico Mosina ◽

Gert T Oostergetel ◽

Raimund Dutzler ◽

...

Keyword(s):

Functional Data ◽

Functional Characterization ◽

Anion Channel ◽

Bound State ◽

Common Mechanism ◽

Protein Conformations ◽

Closed Conformation ◽

Ligand Free ◽

The Relationship

The lipid scramblase TMEM16F initiates blood coagulation by catalyzing the exposure of phosphatidylserine in platelets. The protein is part of a family of membrane proteins, which encompasses calcium-activated channels for ions and lipids. Here, we reveal features of murine TMEM16F (mTMEM16F) that underlie its function as a lipid scramblase and an ion channel. The cryo-EM data of mTMEM16F in absence and presence of Ca2+ define the ligand-free closed conformation of the protein and the structure of a Ca2+-bound intermediate. Both conformations resemble their counterparts of the scrambling-incompetent anion channel mTMEM16A, yet with distinct differences in the region of ion and lipid permeation. In conjunction with functional data, we demonstrate the relationship between ion conduction and lipid scrambling. Although activated by a common mechanism, both functions appear to be mediated by alternate protein conformations that are at equilibrium in the ligand-bound state.

Download Full-text

Interstellar gas in the central region of the Galaxy

Symposium - International Astronomical Union ◽

10.1017/s0074180900101032 ◽

1967 ◽

Vol 31 ◽

pp. 239-251 ◽

Cited By ~ 3

Author(s):

F. J. Kerr

Keyword(s):

Central Region ◽

Galactic Plane ◽

Neutral Hydrogen ◽

Continuum Emission ◽

Galactic Centre ◽

Interstellar Gas ◽

Hydrogen Recombination ◽

The Galaxy ◽

Centre Region ◽

The Relationship

A review is given of information on the galactic-centre region obtained from recent observations of the 21-cm line from neutral hydrogen, the 18-cm group of OH lines, a hydrogen recombination line at 6 cm wavelength, and the continuum emission from ionized hydrogen.Both inward and outward motions are important in this region, in addition to rotation. Several types of observation indicate the presence of material in features inclined to the galactic plane. The relationship between the H and OH concentrations is not yet clear, but a rough picture of the central region can be proposed.

Download Full-text

The relationship of the scleractinian corals to the rugose corals

Paleobiology ◽

10.1017/s0094837300025707 ◽

1980 ◽

Vol 6 (02) ◽

pp. 146-160 ◽

Cited By ~ 29

Author(s):

William A. Oliver

Keyword(s):

Critical Points ◽

Scleractinian Corals ◽

Convincing Evidence ◽

Early Triassic ◽

Rugose Corals ◽

History Of ◽

The Subject ◽

Relationship Of ◽

The Relationship ◽

Biologic Factors

The Mesozoic-Cenozoic coral Order Scleractinia has been suggested to have originated or evolved (1) by direct descent from the Paleozoic Order Rugosa or (2) by the development of a skeleton in members of one of the anemone groups that probably have existed throughout Phanerozoic time. In spite of much work on the subject, advocates of the direct descent hypothesis have failed to find convincing evidence of this relationship. Critical points are:(1) Rugosan septal insertion is serial; Scleractinian insertion is cyclic; no intermediate stages have been demonstrated. Apparent intermediates are Scleractinia having bilateral cyclic insertion or teratological Rugosa.(2) There is convincing evidence that the skeletons of many Rugosa were calcitic and none are known to be or to have been aragonitic. In contrast, the skeletons of all living Scleractinia are aragonitic and there is evidence that fossil Scleractinia were aragonitic also. The mineralogic difference is almost certainly due to intrinsic biologic factors.(3) No early Triassic corals of either group are known. This fact is not compelling (by itself) but is important in connection with points 1 and 2, because, given direct descent, both changes took place during this only stage in the history of the two groups in which there are no known corals.

Download Full-text

Choosing a Markov blanket

Behavioral and Brain Sciences ◽

10.1017/s0140525x19002632 ◽

2020 ◽

Vol 43 ◽

Author(s):

Thomas Parr

Keyword(s):

Markov Blanket ◽

Target Article ◽

The Relationship

Abstract This commentary focuses upon the relationship between two themes in the target article: the ways in which a Markov blanket may be defined and the role of precision and salience in mediating the interactions between what is internal and external to a system. These each rest upon the different perspectives we might take while “choosing” a Markov blanket.

Download Full-text