Mechanism of anion-cation selectivity of amphotericin B channels

Borisova, M. P.; Brutyan, Rafik A.; Ermishkin, L. N.

doi:10.1007/bf01869681

Cited by 51 publications

(32 citation statements)

References 9 publications

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“…The addition to the membrane bathing solution of phloretin, which is known to decrease the membrane dipole potential [23], [24], produced a significant decrease of the channel conductance (by factor of 3), while the pore conductance increased by ∼1.5 in the presence of RH 421, known to increase ϕ d [25]. For preferentially anion-conductive AmB-channels [26] one could expect that a decrease of ϕ d would produce a decrease of the pore conductance [23], [27]. We have previously observed similar effects of these dipole modifiers on predominantly anion-selective syringomycin E channels [28].…”

Section: Resultsmentioning

confidence: 99%

“…The exact molecular architecture of the AmB channel is under debate; different models for the formation and structure of the AmB channel have been proposed. The most popular is the sterol-dependent double-pore model: the two-sided effect of polyene antibiotic results from the association of AmB with sterol molecules and the formation of anion-selective symmetric barrel stave pores made from two “half-pores” in opposite monolayers [3]–[6].…”

Section: Introductionmentioning

confidence: 99%

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Probing Amphotericin B Single Channel Activity by Membrane Dipole Modifiers

2012

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The effects of dipole modifiers and their structural analogs on the single channel activity of amphotericin B in sterol-containing planar phosphocholine membranes are studied. It is shown that the addition of phloretin in solutions bathing membranes containing cholesterol or ergosterol decreases the conductance of single amphotericin B channels. Quercetin decreases the channel conductance in cholesterol-containing bilayers while it does not affect the channel conductance in ergosterol-containing membranes. It is demonstrated that the insertion of styryl dyes, such as RH 421, RH 237 or RH 160, in bilayers with either cholesterol or ergosterol leads to the increase of the current amplitude of amphotericin B pores. Introduction of 5α-androstan-3β-ol into a membrane-forming solution increases the amphotericin B channel conductance in a concentration-dependent manner. All the effects are likely to be attributed to the influence of the membrane dipole potential on the conductance of single amphotericin B channels. However, specific interactions of some dipole modifiers with polyene-sterol complexes might also contribute to the activity of single amphotericin B pores. It has been shown that the channel dwell time increases with increasing sterol concentration, and it is higher for cholesterol-containing membranes than for bilayers including ergosterol, 6-ketocholestanol, 7-ketocholestanol or 5α-androstan-3β-ol. These findings suggest that the processes of association/dissociation of channel forming molecules depend on the membrane fluidity.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Probing Amphotericin B Single Channel Activity by Membrane Dipole Modifiers

2012

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“…Metabolic disruption and cell death are consequent upon membrane alterations. Investigations of the sterol content of mutant strains of Candida albicans and Cryptococcus neoformans has demonstrated that resistance is often associated with alterations in membrane sterol composition (7,21,22 (11)(12)(13)(14)(15)(16)(17)(18)(19) . Resistance to amphotericin B is rare, but is noteworthy for Pesudallescheria boydii, Fusarium spp, and Trichosporon spp.…”

Section: Amphotericin Bmentioning

confidence: 99%

“…A major advance in the use of this agent has resulted from an understanding of the mechanism of its renal toxicity, which is presumed to involve tubuloglomerular feedback. The suppression of glomerular filtration could be reduced by administering sodium chloride (11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22).…”

Section: Amphotericin Bmentioning

confidence: 99%

Antifungal agents: Polyene, azole, antimetabolite, other and future agents

Malayeri

Rezaei

Raiesi

2018

JBRMS

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Antifungals have always been considered as one of the astonishing discoveries of the 20th century. This is correct, but the real marvel is the development of antifungal resistance in hospitals, communities, and the environment concomitant with their use. Fungal infections have emerged as an important clinical threat, with significant associated morbidity and mortality. This study is designed to provide a comprehensive view of antifungal agents and related agents. Information was based on the expertise of some literatures. Over the past decades, the incidence and diversity of fungal infection has grown in association with an increasing number of immunocompromised patients. An understanding of the pharmacokinetic and pharmacodynamics properties of the classes of antifungal compounds is vital for the effective management of invasive fungal infections. This review provides a summary of the pharmacologic principles involved in treatment of fungal diseases. Clinical needs for novel antifungal agents have altered steadily with the rise and fall of AIDS-related mycoses, and the change in spectrum of fatal disseminated fungal infections that has accompanied change in therapeutic immunosuppressive therapies.

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“…noted also in certain other channels that allow both cation and anion entry ( Borisova et al, 1986 ;Franciolini and Nonner, 1994a,b ).…”

Section: What Difference Does It Make For Cell Signaling?mentioning

confidence: 99%

Connexin Specificity of Second Messenger Permeation: Real Numbers At Last

Harris¹

2008

J Cell Biol

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Correspondence to a h a r r i s @ u m d n j . e d uThe discovery many years ago that ions and cytoplasmic molecules could diffuse between cells via gap junction channels inspired excited speculation about the roles such intercellular communication could play in development, physiology, and pathology. This view was reinforced when it later emerged that there are many types of gap junction channels, with ‫ف‬ 20 functionally distinct vertebrate isoforms of the component protein (connexin), which can combine in homomeric and heteromeric channel structures that have distinct conductance, dye permeability, and gating properties. The unitary conductances range from 10 pS to 300 pS; their cation/ anion permeability ratios ( P K+ / P Cl -) range from ‫ف‬ 8.0 to ‫ف‬ 0.8 and their permeabilities to fl uorescent tracers are highly disparate. None of these parameters correlate with each other ( Harris, 2001 ).What is all this variability good for? It seems unlikely to be all about electrical coupling; it makes more sense to think that the distinct pore/permeability properties are important and perhaps designed for the ability to defi ne, mediate, and dynamically modulate the vocabulary of intercellular molecular signals.In fact, evidence for the importance of gap junction as conduits of intercellular molecular signals is growing. In recent years it has been demonstrated, in mostly qualitative ways, that different types of connexin channels have different effective permeabilities to specifi c cytoplasmic molecules, and that the permeability differences among connexin channels cannot be readily inferred from other known functional features. This work has increased speculation that (a) the pores of connexin channels are fi ne tuned for selectivity among specifi c cytoplasmic molecules, and (b) the connexin channels expressed at a particular cellular or tissue location are functionally selected for the ability to mediate highly specifi c intercellular signaling (i.e., for permeability to a specifi c second messenger, or for a specifi c spectrum of permeabilities among a set of second messengers).Several studies have inferred or determined perchannel permeabilities to second messengers, but quantitative data directly comparing the permeabilities of different junctional connexin channels to a second messenger have been lacking. The paper by Kanaporis et al. in this issue (see p. 2 9 3 ) provides such information; it reports the relative and absolute per-channel permeabilities to cAMP of junctional channels formed by three different connexins (Cx26, Cx40, and Cx43). In addition, they provide, for each connexin studied, a quantitative relation between junctional conductance and cAMP permeability and between permeability to the dye Lucifer yellow (LY) and permeability to cAMP. This information permits junctional conductance or LY permeability to be used to quantitatively estimate the corresponding junctional permeability to cAMP (which of course is far more diffi cult to measure). In addition, the cAMP/K + and LY/K + permeability rat...

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Mechanism of anion-cation selectivity of amphotericin B channels

Cited by 51 publications

References 9 publications

Probing Amphotericin B Single Channel Activity by Membrane Dipole Modifiers

Probing Amphotericin B Single Channel Activity by Membrane Dipole Modifiers

Antifungal agents: Polyene, azole, antimetabolite, other and future agents

Connexin Specificity of Second Messenger Permeation: Real Numbers At Last

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