Heteromultimeric ion channel receptor and uses thereof

Details Heteromultimeric ion channel receptor and uses thereof Heteromultimeric ion channel receptor and uses thereof

2001-04-20

2009-06-16

Pak, Michael (Department: 1646)

Chemistry: molecular biology and microbiology

Measuring or testing process involving enzymes or...

Involving antigen-antibody binding, specific binding protein...

C530S350000

Reexamination Certificate

active

07547521

ABSTRACT:
The present invention describes a heteromultimeric proton-gated ion channel (herein called ASIC-2S.2) with distinctive properties. Compositions and methods are provided for producing and expressing functional ASIC-2S.2 channels, composed of ASIC2A and ASIC3 subunits. The invention also provides genetically engineered expression vectors comprising the nucleic acid sequences encoding both ASIC2A and ASIC3 and host cells coexpressing both ASIC2A and ASIC3 subunits. Also provided herein are genetically engineered nucleic acids encoding chimeric proton-gated ion channels comprised of at least two different subunits, as well as expression vectors and host cells comprising said engineered nucleic acids. The invention also provides for the use of ASIC-2S.2, as well as agonists, antagonists or antibodies specifically binding ASIC-2S.2, in the diagnosis, prevention and treatment of diseases associated with expression of ASIC-2S.2. Also are disclosed methods of influencing electrophysiological, pharmacological and/or functional properties of ASIC-2S.2 as well as methods for screening for substances having ion-channel modulating activity or substances capable of disrupting subunit association or interaction.

REFERENCES:
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Bowie et al., 1990, Science 247:1306-1310.
K. Babinski, et al., “Mamalian ASIC2a and ASIC3 Subunits Co-assemble into Heteromeric Proton-gated Channels Sensitive to Gd3+,” J. Biol. Chem. 275(37):28519-28525, 2000.
N. Le Novere and J.-P. Changeux, “The Ligand Gated Ion Channel Database,” Nucl. Acids Res. 27(1):340-344, 1999.
S. J. Perry, et al., “A Human Gene Encoding Morphine Modulating Peptides Related to NPFF and FMRFamide,” FEBS Let. 409:426-430, 1997.
T. Volk, et al., “Hypertonicity Activates Nonselective Cation Channels in Mouse Cortical Collecting Duct Cells,” Proc. Natl. Acad. Sci. USA 92:8478-8482, 1995.

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