The Metrohealth System

Chantest, Inc.

Other

The United States of America, As Represented by the Secretary, Department of Health and Human Services

Case Western Reserve University

The United States of America

Chanrx Corp.

Arthur M Brown

Barbara A Wible

Naresh Chand

Qing Yang

Eckhard Ficker

Kai S Lee

Norio Akaike

Disclosed are methods of preventing or treating cardiac arrhythmia comprising administering to a mammal in need thereof, such as a human, an effective amount of vanoxerine (GBR 12909) or a pharmaceutically acceptable salt, derivative or metabolite thereof.

Methods for reducing the recurrence of cardiac arrhythmia

Methods of inducing apoptosis in hyperproliferative cells, particularly cancer cells are provided. Such method involves increasing the levels of a potassium channel modulatory protein in the cell. Examples of such proteins are native KChAP protein, a biologically active variant of native KChAP protein, or a biologically active KChAP-related protein (collectively referred to hereinafter as 'KChAP protein'). In one embodiment, the cells are contacted with the KChAP protein under conditions permitting uptake of the protein by the cells. In another embodiment, the cells are contacted with (i) a nucleic acid encoding the KChAP protein, and (ii) a promoter active in the cancer cell, wherein the promoter is operably linked to the region encoding the KChAP protein, under conditions permitting the uptake of the nucleic acid by the cancer cell. Methods of detecting cancerous cells in a biological sample selected from the group consisting of a colorectal tissue sample or brain tissue sample are also provided. Such method comprises assaying for the presence of elevated levels of KChAP mRNA or KChAP protein in the sample.

Methods of inducing apoptosis in hyperproliferative cells

Methods for treating cardiac arrhythmia

Disclosed are high throughput assay systems and methods for identifying agents that alter the level of expression of proteins in mammalian cells, particularly integral membrane proteins.

High throughput assay systems and methods for identifying agents that alter expression of cellular proteins

Disclosed are high throughput assay systems and methods for identifying agents that alter the level of surface expression of integral membrane proteins, such as cardiac ion channels, in mammalian cells. Also disclosed are therapeutic methods of using agents identified using such methods.

High throughput assay systems and methods for identifying agents that alter surface expression of integral membrane proteins

The present invention provides polynucleotides that encode a protein, designated herein as K+ Channel Associated Protein or 'KChAP'. It has been determined that expressing polynucleotides that encode KChAP in host cells, along with polynucleotides that encode the Kv&#x3b1; channel subunit Kv 2.1, the Kv&#x3b1; channel subunit Kv 2.2, the Kv&#x3b1; channel subunit Kv 1.3, or the Kv&#x3b1; channel subunit Kv 4.3, increases the number of Kv2.1, Kv 2.2, Kv1.3 or Kv4.3 channels, respectively, in the plasma membrane of such cells. The present invention also relates to a method of making cells that have increased numbers of Kv channels on the plasma membranes thereof and to a method of using such cells as model systems for studying the effect of pharmacological agents on Kv channels, particularly on Kv2.1, Kv 2.2, Kv 1.3, and Kv 4.3 channels. The present invention also relates to the protein KChAP.

Protein that enhances expression of potassium channels on cell surfaces and nucleic acids that encode the same

The present invention provides polynucleotides that encode a protein, designated herein as K&plus; Channel Associated Protein or &ldquo;KChAP&rdquo;. It has been determined that expressing polynucleotides that encode KChAP in host cells, along with polynucleotides that encode the Kv&agr; channel subunit Kv 2.1, the Kv&agr; channel subunit Kv 2.2, the Kv&agr; channel subunit Kv 1.3, or the Kv&agr; channel subunit Kv 4.3, increases the number of Kv2.1, Kv 2.2, Kv1.3 or Kv4.3 channels, respectively, in the plasma membrane of such cells. The present invention also relates to a method of making cells that have increased numbers of Kv channels on the plasma membranes thereof and to a method of using such cells as model systems for studying the effect of pharmacological agents on Kv channels, particularly on Kv2.1, Kv 2.2, Kv 1.3, and Kv 4.3 channels. The present invention also relates to the protein KChAP.

The present invention provides a novel treatment for cardiac arrhythmias, by administering S-adenosyl methionine decarboxylase inhibitors, preferably 5'-({(Z)-4-amino-2-butenyl}methylamino)-5'-deoxyadenosine. It has been discovered that 5'-({(Z)-4-amino-2-butenyl}methylamino)-5'-deoxyadenosine, increases the P--R interval, increases outward current through inward rectifier K.sup.+ channels and increases the hyperpolarization, of cardiac cells, thereby reducing cardiac excitability. Specifically, the method involves providing an S-adenosyl methionine decarboxylase inhibitor; combining the S-adenosyl methionine decarboxylase inhibitor with a pharmaceutically acceptable carrier to provide a pharmaceutical composition; administering an effective amount of the pharmaceutical composition to a patient suffering from a cardiac arrhythmia, wether such arrhythmias are induced by disease or cardiotoxicity. As a result of the treatment with S-adenosyl methionine decarboxylase inhibitor, spermine and spermidine levels are lowered in cardiac cells, the P--R interval is prolonged, cardiac excitability is reduced and the incidence of ventricular fibrillation, particularly sustained ventricular fibrillation is diminished. The method of the present invention is useful to terminate, prevent or reduce the incidence of cardiac arrhythmias, including, for example, ventricular tachycardia, atrial fibrillation ventricular fibrillation, particularly sustained ventricular fibrillation, and premature ventricular contractions.

Treatment for cardiac arrhythmias

An electrical sensing and stimulation electrode small enough to record intracellular activity within a single living cell. The electrode incorporates a cylindrical chamber with a finely tapered end section. The chamber is evacuated to hold the cell at its tip. Contained within the chamber are piping, circuitry, and controls to provide selected life support environment, stimulation, and continuous sensing of the iternal ionic composition of the captured cell.

Growing community of inventors

Brecksville, OH, United States of America

Arthur M Brown