Inhibition of oxygen consumption in skeletal muscle-derived mitochondria by pinacidil, diazoxide, and glibenclamide, but not by 5-hydroxydecanoate.
Cell intermediary metabolism and energy production succeeds by means of mitochondria, whose activity is in relation to transmembrane potential and/or free radical production. Adenosine triphosphate (ATP)-dependent potassium channels (K(ATP)) in several cell types have shown to couple cell metabolism to membrane potential and ATP production. In this study, we explore whether oxygen consumption in isolated skeletal-muscle mitochondria differs in the presence of distinct respiration substrates and whether these changes are affected by K(ATP)-channel inhibitors such as glibenclamide, 5-Hydroxydecanoate (5-HD), and K(ATP) channel activators (pinacidil and diazoxide). Results demonstrate a concentration-dependent diminution of respiration rate by glibenclamide (0.5-20 microM), pinacidil (1-50 microM), and diazoxide (50-200 microM), but no significant differences were found when the selective mitochondrial K(ATP)-channel inhibitor (5-HD, 10-500 microM) was used. These results suggest that these K(ATP)-channel agonists and antagonists exert an effect on mitochondrial respiration and that they could be acting on mito-K(ATP) or other respiratory-chain components.
Montoya-Pérez
Rocío
R
Unidad de Investigación Enrico Stefani Bonfanti from Centro Universitario de Investigaciones Biomédicas, Universidad de Colima, Av. 25 de Julio #965, Col. Villa San Sebastián, 28016, Colima, Colima, México.
Saavedra-Molina
Alfredo
A
Trujillo
Xóchitl
X
Huerta
Miguel
M
Andrade
Felipa
F
Sánchez-Pastor
Enrique
E
Ortiz
Mónica
M
D000818:Animals; D002645:Chickens; D003652:Decanoic Acids / Q000494:pharmacology; D003981:Diazoxide / Q000494:pharmacology; D005905:Glyburide / Q000494:pharmacology; D006880:Hydroxy Acids / Q000494:pharmacology; D066298:In Vitro Techniques; D008931:Mitochondria, Muscle / Q000187:drug effects* / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism; D010101:Oxygen Consumption / Q000187:drug effects*; D020110:Pinacidil / Q000494:pharmacology; D026902:Potassium Channel Blockers / Q000494:pharmacology; D015221:Potassium Channels / Q000819:agonists / Q000187:drug effects* / Q000378:metabolism*
D003652:Decanoic Acids; D006880:Hydroxy Acids; D026902:Potassium Channel Blockers; D015221:Potassium Channels; C117780:mitochondrial K(ATP) channel; C052853:5-hydroxydecanoic acid; D020110:Pinacidil; D003981:Diazoxide; D005905:Glyburide