973 results about "Ion channel" patented technology

Single-channel thin film devices and methods for using the same are provided. The subject devices comprise cis and trans chambers connected by an electrical communication means. At the cis end of the electrical communication means is a horizontal conical aperture sealed with a thin film that includes a single nanopore or channel. The devices further include a means for applying an electric field between the cis and trans chambers. The subject devices find use in applications in which the ionic current through a nanopore or channel is monitored where such applications include the characterization of naturally occurring ion channels, the characterization of polymeric compounds, and the like.

It has been discovered that the stimulation of beta-adrenergic receptors, which activate cAMP formation, give rise to increased APP and GFAP synthesis in astrocytes. Hence, the in vitro or in vivo exposure of neuronal cells to certain compositions comprising beta-adrenergic receptor ligands or agonists, including, e.g., norepinephrine, isoproterenol and the like, increases APP mRNA transcription and consequent APP overproduction. These increases are blocked by beta-adrenergic receptor antagonists, such as propranolol. The in vitro or in vivo treatment of these cells with 8Br-cAMP, prostaglandin E2 (PG E2), forskolin, and nicotine ditartrate also increased APP synthesis, including an increase in mRNA and holoprotein levels, as well as an increase in the expression of glial fibrillary acidic protein (GFAP). Compositions and methods are disclosed of regulating APP overexpression and mediating reactive astrogliosis through cAMP signaling or the activation of beta-adrenergic receptors. It has further been found that the increase in APP synthesis caused by 8Br-cAMP, PG E2, forskolin, or nicotine ditartrate is inhibited by immunosuppressants or anti-inflammatory agents, such as cyclosporin A, and FK-506 (tacrolimus), as well as ion-channel modulators, including ion chelating agents such as EGTA, or calcium / calmodulin kinase inhibitors, such as KN93. The present invention has broad implications in the alleviation, treatment, or prevention of neurological disorders and neurodegenerative diseases, including Alzheimer's Disease.

The present invention relates to a structure comprising a biological membrane and substrate with fluidic network, an array of membranes and an array of fluidic networks in substrate, a high throughput screen, methods for production of the membrane, substrate structure, and a method for interconnected array of substrate structures and a method for attaching membranes to structure, a method to electrically record events from the membranes and a method to screen large compound library using the array. More particularly, it relates to biological cells and artificial cell membranes adhered to the substrate with a high electrical resistivity seal, a method to manufacture array configuration of such substrates, and a method to screen compounds using the membrane receptors such as ion-channels, ion pumps, & receptors.

Plate and electrode assemblies include configurations allowing for relatively uniform electric field production. The electrodes may comprise strips of conductive material plated onto the bottom surface of sample wells or they may comprise plate electrodes extending down into the well. In some embodiments, the electric field strength varies by less than about 10% from a mean field intensity over at least about 20% of the surface area of the bottom surface of a sample well.

It has been discovered that the stimulation of beta -adrenergic receptors, which activate cAMP formation, give rise to increased APP and GFAP synthesis in astrocytes. Hence, the in vitro or in vivo exposure of neuronal cells to certain compositions comprising beta -adrenergic receptor ligands or agonists, including, e.g., norepinephrine, isoproterenol and the like, increases APP mRNA transcription and consequent APP overproduction. These increases are blocked by beta -adrenergic receptor antagonists, such as propranolol. The in vitro or in vivo treatment of these cells with 8Br-cAMP, prostaglandin E2 (PG E2), forskolin, and nicotine ditartrate also increased APP synthesis, including an increase in mRNA and holoprotein levels, as well as an increase in the expression of glial fibrillary acidic protein (GFAP). Compositions and methods are disclosed of regulating APP overexpression and mediating reactive astrogliosis through cAMP signaling or the activation of beta -adrenergic receptors. It has further been found that the increase in APP synthesis caused by 8Br-cAMP, PG E2, forskolin, or nicotine ditartrate is inhibited by immunosuppressants or anti-inflammatory agents, such as cyclosporin A, and FK-506 (tacrolimus), as well as ion-channel modulators, including ion chelating agents such as EGTA, or calcium / calmodulin kinase inhibitors, such as KN93. The present invention has broad implications in the alleviation, treatment, or prevention of neurological disorders and neurodegenerative diseases, including Alzheimer's Disease.

Stimulation of target cells using light, e.g., in vivo or in vitro, is implemented using a variety of methods and devices. One example involves a vector for delivering a light-activated molecule comprising a nucleic acid sequence that codes for light-activated molecule. The light-activated molecule includes a modification to a location near the all-trans retinal Schiff base, e.g., to extends the duration time of the open state. Other aspects and embodiments are directed to systems, methods, kits, compositions of matter and molecules for ion channels or pumps or for controlling currents in a cell (e.g., in in vivo and in vitro environments).

A secondary battery comprises a negative electrode and a positive electrode which oppose each other and an ion conductive member which includes a layered or columnar structure (ion channels) in its matrix and which is sandwiched between the negative electrode and the positive electrode.

Novel multichannel ionosonic devices with microneedle arrays incorporated into the devices for transdermal and intradermal delivery are described. In an embodiment, the ionosonic device includes a multichannel ionophoretic driver used in combination with a multichannel dispersion electrode integrated with ultrasonic elements and microneedle array elements mounted on a single application electrode. The ionosonic-microneedle transdermal device can be configured in a variety of shapes and structural flexibility for the treatment of skin and systemic disorders through the intradermal and transdermal delivery of one or more of a variety of therapeutic and modulating agents. Because of enhanced transdermal penetration this device offers the transdermal delivery of therapeutic peptides is getting closer to reality. The devices described herein deliver the therapeutic agents to the targeted diseased area as well as systemic levels obviating the need for oral ingestion, the associated side effects and as in the case of peptides bypasses the hydrolyzing digestive enzymes that make such agents ineffective when taken by mouth.

A method of characterizing the biological activity of a candidate compound may include exposing cells to the candidate compound, and then exposing the cells to a repetitive application of electric fields so as to set the transmembrane potential to a level corresponding to a pre-selected voltage dependent state of a target ion channel.

An anti-E1 ion channel antibody or binding fragment thereof, pharmaceutical compositions comprising said antibodies, use of the antibodies and compositions comprising the same, in treatment, for example in the treatment / modulation of pain and processes for generating and preparing said antibodies.

Ion manipulation systems include ion repulsion by an RF field penetrating through a mesh. Another comprises trapping ions in a symmetric RF field around a mesh. The system uses macroscopic parts, or readily available fine meshes, or miniaturized devices made by MEMS, or flexible PCB methods. One application is ion transfer from gaseous ion sources with focusing at intermediate and elevated gas pressures. Another application is the formation of pulsed ion packets for TOF MS within trap array. Such trapping is preferably accompanied by pulsed switching of RF field and by gas pulses, preferably formed by pulsed vapor desorption. Ion guidance, ion flow manipulation, trapping, preparation of pulsed ion packets, confining ions during fragmentation or exposure to ion to particle reactions and for mass separation are disclosed. Ion chromatography employs an ion passage within a gas flow and through a set of multiple traps with a mass dependent well depth.

The present invention relates to a functionally expressed bacterial voltage-sensitive ion-selective channel. The novel channel can be used in conjunction with mammalian ion channel pore-containing regions in assays for screening for compounds that modulate activity of the channel. One bacterial ion channel of the present invention, called NaChBac, is derived from Bacillus halodurans (GenBank#BAB05220 (8)).

A nanopore device includes a membrane having a nanopore extending there through forming a channel from a first side of the membrane to a second side of the membrane. The surface of the channel and first side of the membrane are modified with a hydrophobic coating. A first lipid monolayer is deposited on the first side of the membrane, and a second lipid monolayer is deposited on the second side of the membrane, wherein the hydrophobic coating causes spontaneous generation of a lipid bilayer across the nanopore orifice. Sensing entities, such as a protein ion channel, can be inserted and removed from the bilayer by adjusting transmembrane pressure, and adapter molecules can be electrostatically trapped in the ion channel by applying high transmembrane voltages, while resistance or current flow through the sensing entity can be measured electrically.

A method of modifying the electrophysiological function of an excitable tissue region of an individual is provided. The method includes the step of implanting cells into the excitable tissue region. Each implanted cell is (a) capable of forming gap junctions with at least one cell of the excitable tissue region; and (b) capable of forming a functional ion channel or transporter, wherein the functional ion channel or transporter is capable of modifying the electrophysiological function of the excitable tissue region.

The invention relates to a unique battery having an active, porous membrane and method of making the same. More specifically the invention relates to a sealed battery system having a porous, metal oxide membrane with uniform, physicochemically functionalized ion channels capable of adjustable ionic interaction. The physicochemically-active porous membrane purports dual functions: an electronic insulator (separator) and a unidirectional ion-transporter (electrolyte). The electrochemical cell membrane is activated for the transport of ions by contiguous ion coordination sites on the interior two-dimensional surfaces of the trans-membrane unidirectional pores. The membrane material is designed to have physicochemical interaction with ions. Control of the extent of the interactions between the ions and the interior pore walls of the membrane and other materials, chemicals, or structures contained within the pores provides adjustability of the ionic conductivity of the membrane.

It has been discovered that the stimulation of beta-adrenergic receptors, which activate cAMP formation, give rise to increased APP and GFAP synthesis in astrocytes. Hence, the in vitro or in vivo exposure of neuronal cells to certain compositions comprising beta-adrenergic receptor ligands or agonists, including, e.g., norepinephrine, isoproterenol and the like, increases APP mRNA transcription and consequent APP overproduction. These increases are blocked by beta-adrenergic receptor antagonists, such as propranolol. The in vitro or in vivo treatment of these cells with 8Br-cAMP, prostaglandin E2 (PG E2), forskolin, and nicotine ditartrate also increased APP synthesis, including an increase in mRNA and holoprotein levels, as well as an increase in the expression of glial fibrillary acidic protein (GFAP). Compositions and methods are disclosed of regulating APP overexpression and mediating reactive astrogliosis through cAMP signaling or the activation of beta-adrenergic receptors. It has further been found that the increase in APP synthesis caused by 8Br-cAMP, PG E2, or forskolin is inhibited by immunosuppressants, immunophilin ligands, or anti-inflammatory agents, such as cyclosporin A, and FK-506 (tacrolimus), as well as ion-channel modulators, including ion chelating agents such as EGTA, or calcium / calmodulin kinase inhibitors, such as KN93. The present invention has broad implications in the alleviation, treatment, or prevention of neurological disorders and neurodegenerative diseases, including Alzheimer's Disease.

Apparatus and methods for managing pain uses separate varying electromagnetic fields, with a variety of temporal and amplitude characteristics, which are applied to a particular neural structure to modulate glial and neuronal interactions as a mechanism for relieving chronic pain. In another embodiment, a single composite modulation / stimulation signal which has rhythmically varying characteristics is used to achieve the same results as separate varying electromagnetic fields. Also, disclosed is an apparatus and method for modulating the expression of genes involved in diverse pathways including inflammatory / immune system mediators, ion channels and neurotransmitters, in both the Spinal Cord (SC) and Dorsal Root Ganglion (DRG) where such expression modulation is caused by spinal cord stimulation or peripheral nerve stimulation using the disclosed apparatus and techniques. In one embodiment of multimodal modulation therapy, the prime signal may be monophasic, or biphasic, in which the polarity of the first phase of the biphasic prime signal may be either cathodic or anodic while the tonic signal may be either monophasic, or biphasic, with the polarity of the first phase of the biphasic tonic signal being either cathodic or anodic.

The present invention includes an apparatus, system and method for stochastic sensing of an analyte to a protein pore. The protein pore may be an engineer protein pore, such as an ion channel at temperatures above 55° C. and even as high as near 100° C. The analyte may be any reactive analyte, including chemical weapons, environmental toxins and pharmaceuticals. The analyte covalently bonds to the sensor element to produce a detectable electrical current signal. Possible signals include change in electrical current. Detection of the signal allows identification of the analyte and determination of its concentration in a sample solution. Multiple analytes present in the same solution may also be detected.

A capacitive sensing system is used to measure a time-varying ion current through a channel, such as an ion channel or protein pore. Such a capacitive system does not suffer problems of electrode corrosion and, when used with methods to control a build up of ion concentration, allows the use of measurement volumes around the channel with dimensions on a scale of nanometers.

Methods, compositions, dosing regimes, and routes of administration for the treatment or prevention of arrhythmias. In these methods, early afterdepolarizations and prolongation of QT interval may be reduced or eliminated by administering ion channel modulating compounds to a subject in need thereof. The ion channel modulating compounds may be cycloalkylamine ether compounds, particularly cyclohexylamine ether compounds. Also described are compositions of ion channel modulating compounds and drugs which induce early afterdepolarizations, prolongation of QT interval and / or Torsades de Pointes.

Compounds, compositions and methods are provided which are useful in the treatment of diseases through the inhibition of sodium ion flux through voltage-gated sodium channels. More particularly, the invention provides heterocyclic aryl sulfonamides, compositions and methods that are useful in the treatment of central or peripheral nervous system disorders, particularly pain and chronic pain by blocking sodium channels associated with the onset or recurrence of the indicated conditions. The compounds, compositions and methods of the present invention are of particular use for treating neuropathic or inflammatory pain by the inhibition of ion flux through a voltage-gated sodium channel.

The present invention provides nucleic acid arrays and methods of using the same for detecting or monitoring expression profiles of drug target genes. Non-limiting examples of drug target genes include kinase genes, phosphatase genes, protease genes, G-protein coupled receptor genes, nuclear hormone receptor genes, and ion channel genes. The present invention also provides methods of using nucleic acid arrays for the identification or validation of drugs or drug targets. In one embodiment, a nucleic acid array of the present invention is concentrated with probes for drug target genes. These probes constitute a substantial portion of all of the polynucleotide probes that are stably attached to the nucleic acid array, and can hybridize under stringent or nucleic acid array hybridization conditions to the tiling sequences selected from Attachment C, or the complements thereof.

Ion channel modulating compounds are disclosed. The compounds of the present invention may be incorporated in compositions and kits. The present invention also discloses a variety of in vitro and in vivo uses for the compounds and compositions, including the treatment of arrhythmia and the production of analgesia and local anesthesia.

The present invention includes biochips for the measurement of cellular ion channels and methods of use and manufacture. The biochips of the present invention have enhanced sealing capabilities provided in part by chemically modifying the surface of the biochip surface or substrate or by exposure to an ionized gas. The present invention also includes novel cartridges for biochips.

The present invention relates to a structure comprising a biological membrane and a porous or perforated substrate, a biological membrane, a substrate, a high throughput screen, methods for production of the structure membrane and substrate, and a method for screening a large number of test compounds in a short period. More particularly it relates to a structure comprising a biological membrane adhered to a porous or perforated substrate, a biological membrane capable of adhering with high resistance seals to a substrate such as perforated glass and the ability to form sheets having predominantly an ion channel or transporter of interest, a high throughput screen for determining the effect of test compounds on ion channel or transporter activity, methods for manufacture of the structure, membrane and substrate, and a method for monitoring ion channel or transporter activity in a membrane.

The present invention includes a group of chemical compounds useful as modulators of calcium ion (Ca2+) channels, especially for T-type, N-Type and L-type channels. The present invention also includes pharmaceutical compositions comprising these calcium ion channel modulating agents and methods of using these calcium ion channel modulating agents for the treatment diseases and conditions associated with the calcium ion channels.

A system for high-throughput analysis of membranous samples having ion channels including at least one membranous sample, a multi-compartment structure including an extracellular chamber, an opposing intracellular chamber and a partition separating the extracellular and intracellular chambers, the partition having a plurality of apertures fluidly and electrically coupling the extracellular and intracellular chambers, wherein at least one of the apertures is sealed by the at least one membranous sample, and another of the apertures is unsealed, a electric source configured to apply a current between the extracellular and intracellular chambers, wherein a portion of the current travels through the unsealed aperture, and a current sensor configured to measure the current between the extracellular and intracellular chambers. A method of using the system is also disclosed.

The invention relates to a method for modulating Ca2+-release-activated Ca2+ channels (CRAC) in a cell by administering to the cell a compound of formula (I): or a pharmaceutically acceptable salt, solvate, clathrate, or prodrug thereof wherein X, Y, A, Z, L and n are defined herein.

It has been discovered that the stimulation of beta-adrenergic receptors, which activate cAMP formation, give rise to increased APP and GFAP synthesis in astrocytes. Hence, the in vitro or in vivo exposure of neuronal cells to certain compositions comprising beta-adrenergic receptor ligands or agonists, including, e.g., norepinephrine, isoproterenol and the like, increases APP mRNA transcription and consequent APP overproduction. These increases are blocked by beta-adrenergic receptor antagonists, such as propranolol. The in vitro or in vivo treatment of these cells with 8Br-cAMP, prostaglandin E2 (PG E2), forskolin, and nicotine ditartrate also increased APP synthesis, including an increase in mRNA and holoprotein levels, as well as an increase in the expression of glial fibrillary acidic protein (GFAP). Compositions and methods are disclosed of regulating APP overexpression and mediating reactive astrogliosis through cAMP signaling or the activation of beta-adrenergic receptors. It has further been found that the increase in APP synthesis caused by 8Br-cAMP, PG E2, or forskolin is inhibited by immunosuppressants, immunophilin ligands, or anti-inflammatory agents, such as cyclosporin A, and FK-506 (tacrolimus), as well as ion-channel modulators, including ion chelating agents such as EGTA, or calcium / calmodulin kinase inhibitors, such as KN93. The present invention has broad implications in the alleviation, treatment, or prevention of neurological disorders and neurodegenerative diseases, including Alzheimer's Disease.

Provided are electrokinetically-altered fluids (e.g., gas-enriched (e.g., oxygen-enriched) electrokinetic fluids) comprising an ionic aqueous solution of charge-stabilized oxygen-containing nanostructures in an amount sufficient to provide, upon contact with a cell, modulation of at least one of cellular membrane potential and cellular membrane conductivity. Particular aspects of the present invention provide compositions and methods suitable for modulation of at least one of cellular membrane potential and cellular membrane conductivity. Additional aspects provide compositions and methods suitable for modulating intracellular signal transduction, including modulation of at least one of membrane structure, membrane potential or membrane conductivity, membrane proteins or receptors, ion channels, and calcium dependant cellular messaging systems, comprising use of the inventive electrokinetically altered solutions to impart electrochemical and / or conformational changes in membranous structures (e.g., membrane proteins, receptors and / or other components) including G-protein coupled receptors (GPCRs), G-proteins, and / or intracellular junctions (e.g., tight junctions, gap junctions, zona adherins and desmasomes).