Substitution of bridge carbons for sulphur in calix[4]arene-bis-α-hydroxymethylphosphonic acid transformed mobile carrier into ionic channel accompanied with evoked muscle contraction and impaired neurotransmission powered by membrane action of resulting thiocalix[4]arene-bis-α-hydroxymethylphosphonic acid.

The action of calix[4]arenes C-424, C-425 and C-1193 has been investigated on suspended cholesterol/egg phosphatidylcholine lipid bilayer in a voltage-clamp mode. Comparative analysis with the membrane action by calix[4]arene-bis-α-hydroxymethylphosphonic acid (C-99) has shown that the substitution of bridge carbons for sulphur and addition of another methyl group to two alkyl tales in the lower rim of former dipropoxycalix[4]arene C-99 transformed mobile carrier that C-99 created in lipid bilayer (Shatursky et al., 2014) into a transmembrane pore as exposure of the bilayer membrane to sulphur-containing derivative dibutoxythiocalix[4]arene C-1193 resulted in microscopic transmembrane current patterns indicative of a channel-like mode of facilitated diffusion.

Extracellular membrane vesicles derived from Komagataeibacter oboediens exposed on the International Space Station fuse with artificial eukaryotic membranes in contrast to vesicles of reference bacterium.

Membranous Extracellular Vesicles (EVs) of Gram-negative bacteria are a secretion and delivery system that can disseminate bacterial products and interact with hosts and the environment. EVs of nonpathogenic bacteria deliver their contents by endocytosis into eukaryotic cells, however, no evidence exists for a fusion delivery mechanism. Here, we describe the fusion of exposed to space/Mars-like stressors simulated on the International Space Station vesicles (E-EVs) from Komagataeibacter oboediens to different types of model planar membranes in comparison with the EVs of the ground-based reference strain.

Amphiphilic anti-SARS-CoV-2 drug remdesivir incorporates into the lipid bilayer and nerve terminal membranes influencing excitatory and inhibitory neurotransmission.

Remdesivir is a novel antiviral drug, which is active against the SARS-CoV-2 virus. Remdesivir is known to accumulate in the brain but it is not clear whether it influences the neurotransmission. Here we report diverse and pronounced effects of remdesivir on transportation and release of excitatory and inhibitory neurotransmitters in rat cortex nerve terminals (synaptosomes) in vitro.

The ability of carbon nanoparticles to increase transmembrane current of cations coincides with impaired synaptic neurotransmission.

Here, carbon nanodots synthesized from β-alanine (Ala-CDs) and detonation nanodiamonds (NDs) were assessed using (1) radiolabeled excitatory neurotransmitters L-[C]glutamate, D-[2,3H]aspartate, and inhibitory ones [H]GABA, [H]glycine for registration of their extracellular concentrations in rat cortex nerve terminals; (2) the fluorescent ratiometric probe NR12S and pH-sensitive probe acridine orange for registration of the membrane lipid order and synaptic vesicle acidification, respectively; (3) suspended bilayer lipid membrane (BLM) to monitor changes in transmembrane current. In nerve terminals, Ala-CDs and NDs increased the extracellular concentrations of neurotransmitters and decreased acidification of synaptic vesicles, whereas have not changed sufficiently the lipid order of membrane. Both nanoparticles, Ala-CDs and NDs, were capable of increasing the conductance of the BLM by inducing stable potential-dependent cation-selective pores.

The geometry of diphtheria toxoid CRM197 channel assessed by thiazolium salts and nonelectrolytes.

The geometry of the channel formed by nontoxic derivative of diphtheria toxin CRM197 in lipid bilayer was determined using the dependence of single-channel conductance upon the hydrodynamic radii of different nonelectrolytes. It was found that the cis entrance of CRM197 channel on the side of membrane to which the toxoid was added at pH 4.8 and the trans entrance on the opposite side at pH 6.

Membrane action of polyhexamethylene guanidine hydrochloride revealed on smooth muscle cells, nerve tissue and rat blood platelets: A biocide driven pore-formation in phospholipid bilayers.

A well-known cationic biocide of guanidine polymer family, polyhexamethylene guanidine hydrochloride (PHMG) has been tested against smooth muscle cells isolated from swine myometrium, synaptosomes of rat brain nerve terminals and rat blood platelets for the membrane action. It was established that PHMG blocked the activity of Na,K-ATPase of smooth muscle cells plasma membrane by 82.2 ± 0.

Anion carrier formation by calix[4]arene-bis-hydroxymethylphosphonic acid in bilayer membranes.

The action of calix[4]arenes C-91, C-97, C-99, C-107 and C-160 on solvent-containing planar bilayer membranes made of cholesterol and egg phosphatidylcholine (egg PC) or synthetic 18-carbon-tail phospholipid DOPC has been investigated in a voltage-clamp mode. Within the range of calix[4]arenes tested, a steady-state voltage-dependent transmembrane current was achieved only after addition of calix[4]-arene C-99 (calix[4]arene-bis-hydroxymethylphosphonic acid) from the side of the membrane the positive potential was applied to. This current exhibited anion selectivity passing more chloride at negative potentials applied from the side of the membrane to which calix[4]arene C-99 was introduced.

Long open amphotericin channels revealed in cholesterol-containing phospholipid membranes are blocked by thiazole derivative.

The action of antifungal drug, amphotericin B (AmB), on solvent-containing planar lipid bilayers made of sterols (cholesterol, ergosterol) and synthetic C14-C18 tail phospholipids (PCs) or egg PC has been investigated in a voltage-clamp mode. Within the range of PCs tested, a similar increase was achieved in the lifetime of one-sided AmB channels in cholesterol- and ergosterol-containing membranes with the C16 tail PC, DPhPC at sterol/DPhPC molar ratio ≤1. The AmB channel lifetimes decreased only at sterol/DPhPC molar ratio >1 that occurred with sterol/PC molar ratio of target cell membranes at a pathological state.

The geometry of the ionic chànnel lumen formed by alpha-latroinsectotoxin from black widow spider venom in the bilayer lipid membranes.

The dependence of single channel conductance formed by alpha-latroinsectotoxin (alpha-LIT) from black widow spider venom in the planar phospholipid membrane on the hydrodynamic radii of different nonelectrolytes allowed to determine the geometry of alpha-LIT water lumen. It was found that the cis- and trans-entrances of alpha-LIT channel had the same effective radii of 0.55-0.

Vitamin B1 thiazole derivative reduces transmembrane current through ionic channels formed by toxins from black widow spider venom and sea anemone in planar phospholipid membranes.

The vitamin B1 (thiamine) structural analogue 3-decyloxycarbonylmethyl-4-methyl-5-(beta-hydroxyethyl) thiazole chloride (DMHT) (0.1 mM) reversibly reduced transmembrane currents in CaCl2 and KCl solutions via ionic channels produced by latrotoxins (alpha-latrotoxin (alpha-LT) and alpha-latroinsectotoxin (alpha-LIT)) from black widow spider venom and sea anemone toxin (RTX) in the bilayer lipid membranes (BLMs). Introduction of DMHT from the cis-side of BLM bathed in 10 mM CaCl2 inhibited transmembrane current by 31.

Clostridium perfringens beta-toxin forms potential-dependent, cation-selective channels in lipid bilayers.

Recombinant beta-toxin from Clostridium perfringens type C was found to increase the conductance of bilayer lipid membranes (BLMs) by inducing channel activity. The channels exhibited a distribution of conductances within the range of 10 to 380 pS, with the majority of the channels falling into two categories of conductance at 110 and 60 pS. The radii of beta-toxin pores found for the conductance states of 110 and 60 pS were 12.

The mechanism of pore assembly for a cholesterol-dependent cytolysin: formation of a large prepore complex precedes the insertion of the transmembrane beta-hairpins.

Perfringolysin O (PFO) is a member of the cholesterol-dependent cytolysin (CDC) family of membrane-penetrating toxins. The CDCs form large homooligomers (estimated to be comprised of up to 50 CDC monomers) that are responsible for generating a large pore in cholesterol-containing membranes of eukaryotic cells. The assembly of the PFO cytolytic complex was examined to determine whether it forms an oligomeric prepore complex on the membrane prior to the insertion of its membrane-spanning beta-sheet.

The mechanism of membrane insertion for a cholesterol-dependent cytolysin: a novel paradigm for pore-forming toxins.

Perfringolysin O (PFO), a water-soluble monomeric cytolysin secreted by pathogenic Clostridium perfringens, oligomerizes and forms large pores upon encountering cholesterol-containing membranes. Whereas all pore-forming bacterial toxins examined previously have been shown to penetrate the membrane using a single amphipathic beta hairpin per polypeptide, cysteine-scanning mutagenesis and multiple independent fluorescence techniques here reveal that each PFO monomer contains a second domain involved in pore formation, and that each of the two amphipathic beta hairpins completely spans the membrane. In the soluble monomer, these transmembrane segments are folded into six alpha helices.

Monoclonal antibodies can uncouple the main alpha-latrotoxin effects: toxin-induced Ca2+ influx and stimulated neurotransmitter release.

A panel of monoclonal antibodies has been produced against alpha-latrotoxin using black widow spider venom. Five of them were characterized relative to their affinity for alpha-latrotoxin and ability to modify the main toxin effects--to increase calcium permeability of synaptosomes, to stimulate the neurotransmitter release and to form the ion channels in artificial lipid membrane. The results reported here show that: (i) the monoclonal antibodies do not alter the alpha-latrotoxin affinity for the membrane acceptor; (ii) two monoclonal antibodies, A6 and A24, can simultaneously inhibit the alpha-latrotoxin induced Ca2+ uptake and GABA release; (iii) monoclonal antibodies A4 completely block the toxin-induced Ca2+ uptake, but decrease partially the rate of GABA release; (iv) monoclonal antibodies A15 that do not modify the alpha-latrotoxin ability to stimulate Ca2+ uptake and GABA release are able to alter the properties of channels formed by the toxin in the artificial lipid bilayer.