Cloning and functional expression of a rat heart KATP channel.

Abstract

Potassium channels that are ATP-sensitive (KATP) couple membrane potential to the metabolic status of the cell. KATP channels are inhibited by intracellular ATP and are stimulated by intracellular nucleotide diphosphates. KATP channels are important regulators of secretory processes and muscle contraction, and are targets for therapeutic treatment of type II diabetes by the inhibitory sulphonylureas and for hypertension by activators such as pinacidil. In cardiac tissue, KATP channels are central regulators of post-ischaemic cardioprotection. Electrophysiological and pharmacological characteristics vary among KATP channels recorded from diverse tissues suggesting extensive molecular heterogeneity. A complementary DNA encoding a KATP channel was isolated from rat heart using the polymerase chain reaction. We report here that the expressed channels possess all of the essential features of native cardiac KATP channels, including sensitivity to intracellular nucleotides. In addition the cloned channels are activated by the potassium channel opener, pinacidil, but are not inhibited by the sulphonylurea, glibenclamide.

• Authors: M L Ashford, C T Bond, T A Blair, J P Adelman
• Journal: Nature (Nature) Vol. 370 Issue 6489 Pg. 456-9 (Aug 11 1994) ISSN: 0028-0836 [Print] England
• PMID: 8047164 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Retracted Publication)

Chemical References

• Guanidines
• Potassium Channels
• Pinacidil
• Adenosine Triphosphate
• Glyburide

Topics

• Adenosine Triphosphate (metabolism)
• Amino Acid Sequence
• Animals
• Cell Line
• Cloning, Molecular
• Cricetinae
• Glyburide (pharmacology)
• Guanidines (pharmacology)
• Humans
• Ion Channel Gating (drug effects)
• Membrane Potentials
• Molecular Sequence Data
• Myocardium (metabolism)
• Organ Specificity
• Pinacidil
• Polymerase Chain Reaction
• Potassium Channels (drug effects, genetics, metabolism)
• Rats
• Sequence Homology, Amino Acid