Search results for "ion channels"
showing 10 items of 137 documents
Ion transport and selectivity in nanopores with spatially inhomogeneous fixed charge distributions
2007
Polymeric nanopores with fixed charges show ionic selectivity when immersed in aqueous electrolyte solutions. The understanding of the electrical interaction between these charges and the mobile ions confined in the inside nanopore solution is the key issue in the design of potential applications. The authors have theoretically described the effects that spatially inhomogeneous fixed charge distributions exert on the ionic transport and selectivity properties of the nanopore. A comprehensive set of one-dimensional distributions including the skin, core, cluster, and asymmetric cases are analyzed on the basis of the Nernst-Planck equations. Current-voltage curves, nanopore potentials, and tr…
Peptides Derived from Apoptotic Bax and Bid Reproduce the Poration Activity of the Parent Full-Length Proteins
2005
Bax and Bid are proapoptotic proteins of the Bcl-2 family that regulate the release of apoptogenic factors from mitochondria. Although they localize constitutively in the cytoplasm, their apoptotic function is exerted at the mitochondrial outer membrane, and is related to their ability to form transbilayer pores. Here we report the poration activity of fragments from these two proteins, containing the first alpha-helix of a colicinlike hydrophobic hairpin (alpha-helix 5 of Bax and alpha-helix 6 of Bid). Both peptides readily bind to synthetic lipid vesicles, where they adopt predominantly alpha-helical structures and induce the release of entrapped calcein. In planar lipid membranes they fo…
Molecular and topological membrane folding determinants of transient receptor potential vanilloid 2 channel.
2015
Transient Receptor Potential (TRP) channels are related to adaptation to the environment and somatosensation. The transient receptor potential vanilloid (TRPV) subfamily includes six closely evolutionary related ion channels sharing the same domain organization and tetrameric arrangement in the membrane. In this study we have characterized biochemically TRPV2 channel membrane protein folding and transmembrane (TM) architecture. Deleting the first N-terminal 74 residues preceding the ankyrin repeat domain (ARD) show a key role for this region in targeting the protein to the membrane. We have demonstrated the co-translational insertion of the membrane-embedded region of the TRPV2 and its disp…
Cluster organization and pore structure of ion channels formed by beticolin 3, a nonpeptidic fungal toxin
1999
Beticolin 3 (B3) belongs to a family of nonpeptidic phytotoxins produced by the fungus Cercospora beticola, which present a broad spectrum of cytotoxic effects. We report here that, at cytotoxic concentration (10 microM), B3 formed voltage-independent, weakly selective ion channels with multiple conductance levels in planar lipid bilayers. In symmetrical standard solutions, conductance values of the first levels were, respectively, 16 +/- 1 pS, 32 +/- 2 pS, and 57 +/- 2 pS (n = 4) and so on, any conductance level being roughly twice the lower one. Whether a cluster organization of elementary channels or different channel structures underlies this particular property was addressed by investi…
Complement lysis: a hole is a hole.
1991
recent experimental advances 21, it is now possible to produce MACs with a precise molecular composition 7 for better designed experiments. In my judgement, however, it will always be problematic to propose a single unifying mechanism for MAC action simply because MAC effects are not uniform. The reason for attempting to classify MACs as leaky patch or channel formers is a desire to wield Occam's razor and carve out the simplest unifying theory. But this razor often cuts one's throat, especially when it comes to immunological processes. A system that degranulates platelets, 'kills' such widely diverse targets as artificial liposomes, 'dead' viruses and erythrocytes, metabolically active cel…
Killer-toxin-resistant kre12 mutants of Saccharomyces cerevisiae: genetic and biochemical evidence for a secondary K1 membrane receptor.
1995
The Saccharomyces cerevisiae killer toxin K1 is a secreted alpha/beta-heterodimeric protein toxin that kills sensitive yeast cells in a receptor-mediated two-stage process. The first step involves toxin binding to beta-1,6-D-glucan-components of the outer yeast cell surface; this step is blocked in yeast mutants bearing nuclear mutations in any of the KRE genes whose products are involved in synthesis and/or assembly of cell wall beta-D-glucans. After binding to the yeast cell wall, the killer toxin is transferred to the cytoplasmic membrane, subsequently leading to cell death by forming lethal ion channels. In an attempt to identify a secondary K1 toxin receptor at the plasma membrane leve…
Current rectification by nanoparticle blocking in single cylindrical nanopores.
2014
Blocking of a charged pore by an oppositely charged nanoparticle can support rectifying properties in a cylindrical nanopore, as opposed to the usual case of a fixed asymmetry in the pore geometry and charge distribution. We present here experimental data and model calculations to confirm this fundamental effect. The nanostructure imaging and the effects of nanoparticle concentration, pore radius, and salt concentration on the electrical conductance–voltage (G–V) curves are discussed. Logic responses based on chemical and electrical inputs/outputs could also be implemented with a single pore acting as an effective nanofluidic diode. To better show the generality of the results, different ch…
Co-expression of heat sensitive vanilloid receptor subtypes in rat dorsal root ganglion neurons
2003
Expression of the heat sensitive cation channels TRPV1 and TRPV2 was investigated by immunofluorescence in rat dorsal root ganglion (DRG) neurons. TRPV1-positive neurons were more frequent and had smaller diameters than TRPV2-positive neurons (35.7% vs 7.3%; 22.3 microm vs 27.6 microm), but size distributions overlapped and significant co-expression was seen in 20.7% of TRPV2-positive neurons (1.7% of all). Expression patterns did not differ between tissue sections typically used in immunocytochemistry and dissociated DRG neurons typically used in electrophysiology. Rectangular temperature pulses revealed two patterns of heat-evoked inward currents in small DRG neurons: low-threshold rapidl…
Conformational changes in acetylcholine binding protein investigated by temperature accelerated molecular dynamics.
2014
Despite the large number of studies available on nicotinic acetylcholine receptors, a complete account of the mechanistic aspects of their gating transition in response to ligand binding still remains elusive. As a first step toward dissecting the transition mechanism by accelerated sampling techniques, we study the ligand-induced conformational changes of the acetylcholine binding protein (AChBP), a widely accepted model for the full receptor extracellular domain. Using unbiased Molecular Dynamics (MD) and Temperature Accelerated Molecular Dynamics (TAMD) simulations we investigate the AChBP transition between the apo and the agonist-bound state. In long standard MD simulations, both confo…
Desensitization is a property of the cholinergic binding region of the nicotinic acetylcholine receptor, not of the receptor-integral ion channel
1991
AbstractThe reversible acetylcholine esterase inhibitor (−)-physostigmine (eserine) is the prototype of a new class of nicotinic acetylcholine receptor (nAChR) activating ligands: it induces cation fluxes into nAChR-rich membrane vesicles from Torpedo marmorala electric tissue even under conditions of antagonist blocked acetylcholine binding sites (Okonjo, Kuhlmann, Maclicke, Neuron, in press). This suggests that eserine exerts its channel-activating property via binding sites at the nAChR separate from those of the natural transmitter. We now report that eserine can activate the channel even when the receptor has been preincubated (desensitized) with elevated concentrations of acetylcholin…