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Pacemaker ion channel proteins and uses thereof

Inactive Publication Date: 2005-01-06
THE TRUSTEES OF COLUMBIA UNIV IN THE CITY OF NEW YORK
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0013] Further, the present invention provides a method of identifying a compound which modulates the activity of BCNG-related protein which comprises: (a) introducing the nucleic acid of claim 1 into an expression system and causing the expression system to express the nucleic acid under conditions whereby an ion channel subunit protein is produced; (b) contacting the channe

Problems solved by technology

Unfortunately, this approach is not well suited for identifying more divergent sequences and potentially new branches in the phylogenetic tree of the K+ channel superfamily.

Method used

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  • Pacemaker ion channel proteins and uses thereof
  • Pacemaker ion channel proteins and uses thereof
  • Pacemaker ion channel proteins and uses thereof

Examples

Experimental program
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Effect test

example 1

Interactive Cloning with the SH3 Domain of N-Src Identifies a New Brain-Specific Ion Channel Protein, with Homology to Cyclic Nucleotide-Gated Channels

[0063] By screening for molecules that interact with the neuronal form of Src tyrosine kinase a novel cDNA was isolated that appears to represent a new class of ion channels. The encoded polypeptide, mBCNG-1, is distantly related to proteins in the family of the cyclic nucleotide-gated channels and the voltage-gated channels, Eag and H-erg. mBCNG-1 is expressed exclusively in the brain as a glycosylated protein of approximately 132 kD. Immunohistochemical analysis indicates that mBCNG-1 is preferentially expressed in specific subsets of neurons in the neocortex, hippocampus and cerebellum, in particular pyramidal neurons and basket cells. Within individual neurons, the BCNG-1 protein is localized to either the dendrites or the axon terminals depending on the cell type.

[0064] Southern blot analysis shows that several other BCNG-relat...

example 2

Initial Cloning and Description of the Mouse BCNG Gene Family

[0108] The original sequence in the BCNG family (mBCNG-1) was isolated from a mouse brain cDNA library using yeast two-hybrid interaction cloning with the n-Src tyrosine kinase as a bait as described in Example 1. The DNA and amino acid sequences of this protein are Seq. ID. No.:1 and Seq. ID. No.:2 respectively. Clones comprising two additional genes (mBCNG-2 and mBCNG-3) have been isolated. The DNA and amino acid sequences of mBCNG-2 are Seq. ID. No.:5 and Seq. ID. No.: 6 respectively. The DNA and amino acid sequences of mBCNG-3 are Seq. ID. No.:9 and Seq. ID. No.:10 respectively. A more detailed description of the methods used to identify the sequences reported here are given in the methods section below.

[0109] All of the identified sequences contain the motifs of a voltage gated potassium channel (six transmembrane spanning domains, including a highly basic S4 domain, and a pore region) as well as a distinct cyclic n...

example 3

Physiological and pharmacological significance of mouse and human BCNG channel genes.

[0142] Introduction

[0143] The unique structural features and the tissue distribution of the predicted proteins of the BCNG gene family suggests that they may encode the pacemaker current (variously called Ih, If or Iq) of the heart and brain. Even if the BCNG gene family does not encode the pacemaker current it is likely to be a component of other—perhaps unidentified—ionic current(s) that are important in cardiac renal, hepatic and central nervous system function. Irrespective of the identity of the current(s) that the BCNG proteins contribute to, the unique structural features of the predicted BCNG proteins (the unusual ion conducting pore (P) domain, the highly conserved cyclic nucleotide binding (cnbs) site and the highly conserved and highly charged S4 voltage sensor) indicate that they will be susceptible to multiple drug intervention strategies that target the pore, the cyclic nucleotide bi...

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Abstract

The present invention provides an isolated nucleic acid molecule encoding a brain cyclic nucleotide gated ion channel (BCNG) protein. An isolated BCNG protein is also provided as is a composition comprising a BCNG encoding nucleic acid or protein or a portion thereof. The present invention also provides a method of identifying an ion channel subunit related protein encoding nucleic acid molecule in a sample. The invention further provides a method for evaluating the ability of a compound to modulate an ion channel associated neurological, cardia, or renal condition. The invention also provides a method for evaluating the ability of a compound to interact with a BCNG-related ion channel subunit protein. Additionally, the present invention provides a method for identifying a compound capable of modulating the activity of a BCNG-related protein. The present invention additionally provides a method of treating a cardiac, renal or neurological condition. Finally, the present invention provides an antibody which specifically reacts with BCNG protein.

Description

[0001] Throughout this application, various publications are referenced by author and date. Full citations for these publications may be found listed alphabetically at the end of the specification immediately preceding the Sequence Listing and the claims. The disclosures of these publications in their entireties are hereby incorporated by reference into this application in order to more fully describe the state of the art. BACKGROUND OF THE INVENTION [0002] Introduction [0003] Ion channels are a diverse group of proteins that regulate the flow of ions across cellular membranes. In the nervous system, ion channel activity has evolved into a rapid and accurate system for intercellular communication. The electrical excitability characteristics of each neuron is in part determined by the set of channels it expresses. However, cells are also able to regulate the activity of individual channels in response to physiological or developmental events, and there is growing evidence that ion ch...

Claims

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Application Information

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IPC IPC(8): A61K38/00C07K14/705C07K16/28C12N5/02C12Q1/68
CPCA61K38/00C07K14/705C12Q2600/158C12Q1/6883C07K16/28
Inventor KANDEL, ERICSANTORO, BINABARTSCH, DUSANSIEGELBAUM, STEVENTIBBS, GARETHGRANT, SETH
Owner THE TRUSTEES OF COLUMBIA UNIV IN THE CITY OF NEW YORK
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