Chemistry: molecular biology and microbiology – Animal cell – per se ; composition thereof; process of... – Method of regulating cell metabolism or physiology
Reexamination Certificate
1999-07-23
2001-09-11
Carlson, Karen Cochrane (Department: 1653)
Chemistry: molecular biology and microbiology
Animal cell, per se ; composition thereof; process of...
Method of regulating cell metabolism or physiology
C435S375000, C435S320100, C435S325000, C435S326000, C435S069100, C514S003100, C514S023000, C514S397000
Reexamination Certificate
active
06287859
ABSTRACT:
BACKGROUND OF THE INVENTION
FIELD OF THE INVENTION
The present invention relates to new families of mammalian, notably human and rat, acidity-sensitive ionic channels. More particularly, the invention relates to the identification and molecular characterization in humans and rats of a new family of proton-activated cationic channels, collectively referred to below as ASIC polypeptides, for Acid Sensing Ionic Channel.
The ASIC channels constitute the first members of a group of cationic channels belonging to the family of amiloride-sensitive degenerine sodium channels [
6
,
11
-
14
], which are activated temporarily by extracellular acidification.
Sensitivity to acid is associated with both nociception [
1
] and the transduction of taste [
2
]. The stimulation of sensory neurons by acids is of great importance because acidity accompanies numerous painful inflammatory and ischemic situations. The pain caused by acids is thought to be mediated by the cationic channels present at the level of the sensory neurons which are activated by protons [
3
-
5
]. The biophysical and pharmacological properties of the ASIC channels of the invention are similar to those of the proton-activated cationic channels described in the sensory neurons [
3
,
15
,
16
]. However, as will be seen in the description below, to date there has been no report of ligand-activated ionic channels simpler than the ASIC channels.
SUMMARY OF THE INVENTION
The invention also relates to hybrid cationic channels constituted by the combination of a first protein comprising a proton-activated ionic channel according to the invention with a second proton-activated ionic channel.
The present invention has as its object a nucleic acid molecule coding for a protein constitutung a neuronal neuronal cationic channels that is sensitive to amiloride and activated by protons.
The invention also relates to a vector comprising at least one of the preceding nucleic acid molecules, advantageously combined with suitable control sequences, as well as a procedure for production or expression in a cell host of a protein constituting an ionic channel according to the Invention.
The invention also relates to the transformed cells expressing ASIC cation channels and/or their derivatives obtained according to the preceding methods.
The present invention also relates to application of the ASIC channel for studying pathological modifications that may lead to neuronal degenerations. The invention this also relates to the pharmaceutical preparations comprising as an active ingredient, at least one of these proteins of the invention.
Other characteristics and advantages of the invention will be seen in the description below related to research activities that led to the demonstration and the characterization of the ASIC channel.
This invention can be further understood with reference to the Figures, discussed next and in the Examples.
REFERENCES:
patent: 99/11784 (1999-03-01), None
Babinski et al., “Molecular Cloning and Regional Distribution of a Human Proton Receptor subunit with biphasic functional properties”, Journal of Neurochemistry, vol. 22, No. 1, 1999.
Bassilana Frederic
DeWeille Jan R.
Lazdunski Michel
Rainer Waldmann
Carlson Karen Cochrane
Centre National de la Recherche
Robinson Patricia
Schnader Harrison Segal & Lewis LLP
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