Nucleic acids encoding potassium channels which form inward rect

Details Nucleic acids encoding potassium channels which form inward rect Nucleic acids encoding potassium channels which form inward rect

1996-03-07

1998-04-28

Walsh, Stephen

Chemistry: molecular biology and microbiology

Micro-organism, tissue cell culture or enzyme using process...

Recombinant dna technique included in method of making a...

536 231, 536 235, 435 72, 435325, 530350, C12N 1512, C12N 1563, C12N 510, G01N 3348

Patent

active

057443246

ABSTRACT:
Compositions and methods are provided for producing functional mammalian inward rectifier, G-protein activated potassium channels (Kir3.0 channels). A channel is a multimeric protein comprising one or more Kir3.0 polypeptides, e.g. Kir3.1, Kir3.2, etc., where the polypeptides may be from the same or different species. The functional channel has the distinctive features of an anomalous rectifier, in that it conducts inward but not outward K.sup.+ current; it is blocked by low concentrations of extracellular Cs.sup.+ or Ba.sup.2+ ; and the conductance of the channel does not depend solely on voltage, but on (E--E.sub.K). The ability of the channel to conduct inward K.sup.+ current is modulated by G-proteins, particularly G-proteins of the G.sub.i /G.sub.o family. A number of mammalian cell surface receptors activate G-proteins as a consequence of specific ligand binding. The signal transduction from receptor to Kir3.0 channel is therefore coupled through G-protein intermediates.
The functional Kir3.0 channels are useful in drug screening assays directed to modulation of cellular electrophysiology. Nucleic acids encoding Kir3.0 polypeptides are useful for expression of the gene product, and for identification of homologous genes from other species, as well as other members of the same family of proteins. Expression of the nucleic acids in a heterologous cell, e.g. Xenopus oocyte, confers the ability to cause a change in potassium flow in response to G-protein activation.

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