Carriers and channels: current progress and future prospects

Bell, Thomas W.

doi:10.1016/s1367-5931(98)80108-7

Cited by 15 publications

(3 citation statements)

References 37 publications

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“…Calix[4]arene tetrabutylamide 2 forms an ion channel. Ligand-mediated ion transport across a lipid bilayer is usually attributed to three mechanisms; defect induction, a carrier process, or channel formation. 3d, Dye-release experiments showed that 2 does not induce membrane defects. Both carrier and ion channel mechanisms for H + /Cl - transport are conceivable for a ligand like calix[4]arene tetrabutylamide 2 .…”

Section: Resultsmentioning

confidence: 99%

Ion Channel Formation from a Calix[4]arene Amide That Binds HCl

et al. 2002

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The ion transport activity of calix[4]arene tetrabutylamide 1,3-alt 2 was studied in liposomes, planar lipid bilayers, and HEK-293 cells. These experiments, when considered together with (1)H NMR and X-ray crystallography data, indicate that calix[4]arene tetrabutylamide 2 (1) forms ion channels in bilayer membranes, (2) mediates ion transport across cell membranes at positive holding potential, (3) alters the pH inside liposomes experiencing a Cl(-) gradient, and (4) shows a significant Cl(-)/SO(4)(2)(-) transport selectivity. An analogue, calix[4]arene tetramethylamide 1, self-assembles in the presence of HCl to generate solid-state structures with chloride-filled and water-filled channels. Structureminus signactivity studies indicate that the hydrophobicity, amide substitution, and macrocyclic framework of the calixarene are essential for HCl binding and transport. Calix[4]arene tetrabutylamide 2 is a rare example of an anion-dependent, synthetic ion channel.

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Section: Resultsmentioning

confidence: 99%

Ion Channel Formation from a Calix[4]arene Amide That Binds HCl

et al. 2002

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“…While a detailed account on the application of the aforementioned probes is beyond the scope of this review, a few examples are given which indicate the potential of these synthetic fluorescent probes as ion indicators: The use of BTC and MCC-type probes in investigations of Ca 2+ -dependent exocytosis [19], and rates of K + transport across biological membranes [54], respectively. The monitoring of K + efflux from Sf 9 and Cf1 insect cells using CD-222 [55], the applicability of crown ether derivatives such as C343-crown in ion detection [56], the potential use of 4-(monoaza-18-crown-6-methyl)-7-octadecanoylaminocoumarin in optical fiber fluorescence sensor for the detection of saxitoxin [57], the real-time detection of phosphodiesterase 3':5'-cyclic mononucleotide activity by the Cd 2+ -cylen type anion probe [58], and the demonstration of Mg 2+ buffering mechanisms in PC12 cells using KMG-20 [59].…”

Section: Miscellaneous Coumarin Fluorescent Ion Indicatorsmentioning

confidence: 99%

The Coumarin Moiety as Chromophore of Fluorescent Ion Indicators in Biological Systems

Katerinopoulos

2004

CPD

120

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Fluorescent probes have evolved into an extremely useful tool for the detection of ions in biological systems. The design of ion indicators is based in the proper choice of the ion chelating group as well as the chromophore moiety. The chromophores of choice should fulfill a number of requirements concerning the photostability of the group, the range of the excitation and emission wavelengths of the indicators, the Stokes shift, the fluorescence quantum yield, the excitation and/or emission wavelength shift upon coordination of the probe with its target ion, the lipophilicity of the indicators, and their possible cell toxicity. Coumarin and its analogues have been extensively used in ion detection by incorporation of the coumarin chromophore in the larger indicator framework. Coumarins fulfill all the aforementioned requirements since they are relatively photostable and their excitation and emission maxima, in many cases, are long enough to minimise "background" fluorescence of cellular components, tissues and biological fluids. They exhibit Stokes shifts large enough to avoid significant overlap of the excitation and emission spectra, their fluorescence quantum yields allow for ion detection at low indicator concentrations, and they can be introduced to cells either by microinjection or as membrane permeable derivatives without causing cell death. Synthetic approaches, aiming at the optimisation of indicator properties, have extended the conjugated coumarin system either by introduction of substituents or by expansion of the heterocyclic system. In this review, the basic rationale for the selection of the particular coumarin analogues is analysed, synthetic pathways leading to the desired structures are presented, and properties and relative advantages in the use of these probes are described.

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“…This would presumably involve interaction of anions with the positive end of backbone amide dipoles and the substitution of water-anion H-bonding by anion-NH (backbone) H-bonding. Halide complexation via H-bonding has been demonstrated in artificial receptors in nonaqueous solvents (Bell, 1998;Boerrigter et al, 1998). However, thermodynamic data indicate the transfer of K ϩ from water to formamide (a model of the polypeptide backbone that is capable of H-bonding) is a favorable process (⌬G ϭ Ϫ4 kJ/mol, ⌬H ϭ Ϫ17.9 kJ/mol), whereas transfer of Cl Ϫ is unfavorable (⌬G ϭ ϩ14 kJ/mol, ⌬H ϭ ϩ3.5 kJ/mol) (Cox et al, 1974;Dorman et al, 1996;Marcus, 1997).…”

Section: Introductionmentioning

confidence: 99%

Protonation of Lysine Residues Inverts Cation/Anion Selectivity in a Model Channel

Borisenko

Sansom

Woolley

2000

Biophysical Journal

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A dimeric alamethicin analog with lysine at position 18 in the sequence (alm-K18) was previously shown to form stable anion-selective channels in membranes at pH 7.0 [Starostin, A. V., R. Butan, V. Borisenko, D. A. James, H. Wenschuh, M. S. Sansom, and G. A. Woolley. 1999. Biochemistry. 38:6144-6150]. To probe the charge state of the conducting channel and how this might influence cation versus anion selectivity, we performed a series of single-channel selectivity measurements at different pH values. At pH 7.0 and below, only anion-selective channels were found with P(K(+))/P(Cl(-)) = 0. 25. From pH 8-10, a mixture of anion-selective, non-selective, and cation-selective channels was found. At pH > 11 only cation-selective channels were found with P(K(+))/P(Cl(-)) = 4. In contrast, native alamethicin-Q18 channels (with Gln in place of Lys at position 18) were cation-selective (P(K(+))/P(Cl(-)) = 4) at all pH values. Continuum electrostatics calculations were then carried out using an octameric model of the alm-K18 channel embedded in a low dielectric slab to simulate a membrane. Although the calculations can account for the apparent pK(a) of the channel, they fail to correctly predict the degree of selectivity. Although a switch from cation- to anion-selectivity as the channel becomes protonated is indicated, the degree of anion-selectivity is severely overestimated, suggesting that the continuum approach does not adequately represent some aspect of the electrostatics of permeation in these channels. Side-chain conformational changes upon protonation, conformational changes, and deprotonation caused by permeating cations and counterion binding by lysine residues upon protonation are considered as possible sources of the overestimation.

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Carriers and channels: current progress and future prospects

Cited by 15 publications

References 37 publications

Ion Channel Formation from a Calix[4]arene Amide That Binds HCl

Ion Channel Formation from a Calix[4]arene Amide That Binds HCl

The Coumarin Moiety as Chromophore of Fluorescent Ion Indicators in Biological Systems

Protonation of Lysine Residues Inverts Cation/Anion Selectivity in a Model Channel

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