Interactions of K+ATP channel blockers with Na+/K+-ATPase.
Two K(+) (ATP) channel blockers, 5-hydroxydecanoate (5-HD) and glyburide, are often used to study cross-talk between Na(+)/K(+)-ATPase and these channels. The aim of this work was to characterize the effects of these blockers on purified Na(+)/K(+)-ATPase as an aid to appropriate use of these drugs in studies on this cross-talk. In contrast to known dual effects (activating and inhibitory) of other fatty acids on Na(+)/K(+)-ATPase, 5-HD only inhibited the enzyme at concentrations exceeding those that block mitochondrial K(+) (ATP) channels. 5-HD did not affect the ouabain sensitivity of Na(+)/K(+)-ATPase. Glyburide had both activating and inhibitory effects on Na(+)/K(+)-ATPase at concentrations used to block plasma membrane K(+) (ATP) channels. The findings justify the use of 5-HD as specific mitochondrial channel blocker in studies on the relation of this channel to Na(+)/K(+)-ATPase, but question the use of glyburide as a specific blocker of plasma membrane K(+) (ATP) channels, when the relation of this channel to Na(+)/K(+)-ATPase is being studied.
Liu
Lijun
L
Department of Physiology, Pharmacology, Metabolism, and Cardiovascular Sciences, The University of Toledo College of Medicine, Mail Stop 1008, Health Science Campus, 3000 Arlington Avenue, Toledo, OH 43614-2598, USA.
Gable
Marjorie E
ME
Garlid
Keith D
KD
Askari
Amir
A
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology; D003652:Decanoic Acids / Q000494:pharmacology*; D005905:Glyburide / Q000494:pharmacology*; D006880:Hydroxy Acids / Q000494:pharmacology*; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D054086:KATP Channels / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008297:Male; D026902:Potassium Channel Blockers / Q000494:pharmacology*; D015221:Potassium Channels / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors* / Q000378:metabolism
D000889:Anti-Arrhythmia Agents; D003652:Decanoic Acids; D006880:Hydroxy Acids; D007004:Hypoglycemic Agents; D054086:KATP Channels; D026902:Potassium Channel Blockers; D015221:Potassium Channels; C052853:5-hydroxydecanoic acid; D000254:Sodium-Potassium-Exchanging ATPase; D005905:Glyburide