Identification and properties of a novel intracellular (mitochondrial) ATP-sensitive potassium channel in brain.
Protection of heart against ischemia-reperfusion injury by ischemic preconditioning and K(ATP) channel openers is known to involve the mitochondrial ATP-sensitive K(+) channel (mitoK(ATP)). Brain is also protected by ischemic preconditioning and K(ATP) channel openers, and it has been suggested that mitoK(ATP) may also play a key role in brain protection. However, it is not known whether mitoK(ATP) exists in brain mitochondria, and, if so, whether its properties are similar to or different from those of heart mitoK(ATP). We report partial purification and reconstitution of a new mitoK(ATP) from rat brain mitochondria. We measured K(+) flux in proteoliposomes and found that brain mitoK(ATP) is regulated by the same ligands as those that regulate mitoK(ATP) from heart and liver. We also examined the effects of opening and closing mitoK(ATP) on brain mitochondrial respiration, and we estimated the amount of mitoK(ATP) by means of green fluorescence probe BODIPY-FL-glyburide labeling of the sulfonylurea receptor of mitoK(ATP) from brain and liver. Three independent methods indicate that brain mitochondria contain six to seven times more mitoK(ATP) per milligram of mitochondrial protein than liver or heart.
Bajgar
R
R
Department of Biochemistry and Molecular Biology, OGI School of Science and Engineering, Oregon Health & Science University, Beaverton, Oregon 97006-8921, USA.
Seetharaman
S
S
Kowaltowski
A J
AJ
Garlid
K D
KD
Paucek
P
P
D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology; D001896:Boron Compounds / Q000494:pharmacology; D001921:Brain / Q000378:metabolism*; D019806:Cromakalim / Q000494:pharmacology; D003652:Decanoic Acids / Q000494:pharmacology; D003981:Diazoxide / Q000494:pharmacology; D005456:Fluorescent Dyes / Q000494:pharmacology; D005905:Glyburide / Q000494:pharmacology; D006160:Guanosine Triphosphate / Q000378:metabolism; D006880:Hydroxy Acids / Q000494:pharmacology; D007700:Kinetics; D008024:Ligands; D008099:Liver / Q000378:metabolism; D008565:Membrane Proteins / Q000096:biosynthesis* / Q000737:chemistry*; D008928:Mitochondria / Q000378:metabolism*; D008930:Mitochondria, Liver / Q000378:metabolism; D008954:Models, Biological; D009206:Myocardium / Q000378:metabolism; D010101:Oxygen Consumption; D015221:Potassium Channels / Q000737:chemistry*; D011510:Proteolipids / Q000378:metabolism; D051381:Rats; D013997:Time Factors; D014665:Vasodilator Agents / Q000494:pharmacology
C095489:4,4-difluoro-4-bora-3a,4a-diaza-s-indacene; D000889:Anti-Arrhythmia Agents; D001896:Boron Compounds; D003652:Decanoic Acids; D005456:Fluorescent Dyes; D006880:Hydroxy Acids; D008024:Ligands; D008565:Membrane Proteins; D015221:Potassium Channels; D011510:Proteolipids; D014665:Vasodilator Agents; C117780:mitochondrial K(ATP) channel; C020485:proteoliposomes; D019806:Cromakalim; C052853:5-hydroxydecanoic acid; D006160:Guanosine Triphosphate; D000255:Adenosine Triphosphate; D003981:Diazoxide; D005905:Glyburide