Please use this identifier to cite or link to this item:
Title: The KATP channel opener diazoxide protects cardiac myocytes during metabolic inhibition without causing mitochondrial depolarization or flavoprotein oxidation.
Authors: Lawrence, CL
Billups, B
Rodrigo, GC
Standen, NB
First Published: Oct-2001
Citation: BR J PHARMACOL, 2001, 134 (3), pp. 535-542
Abstract: 1. The K(ATP) channel opener diazoxide has been proposed to protect cardiac muscle against ischaemia by opening mitochondrial K(ATP) channels to depolarize the mitochondrial membrane potential, DeltaPsi(m). We have used the fluorescent dye TMRE to measure DeltaPsi(m) in adult rat freshly isolated cardiac myocytes exposed to diazoxide and metabolic inhibition. 2. Diazoxide, at concentrations that are highly cardioprotective (100 or 200 microM), caused no detectable increase in TMRE fluorescence (n=27 cells). However, subsequent application of the protonophore FCCP, which should collapse DeltaPsi(m), led to large increases in TMRE fluorescence (>300%). 3. Metabolic inhibition (MI: 2 mM NaCN+1 mM iodoacetic acid (IAA) led to an immediate partial depolarization of DeltaPsi(m), followed after a few minutes delay by complete depolarization which was correlated with rigor contracture. Removal of metabolic inhibition led to abrupt mitochondrial repolarization followed in many cells by hypercontracture, indicated by cell rounding and loss of striated appearance. 4. Prior application of diazoxide (100 microM) reduced the number of cells that hypercontracted after metabolic inhibition from 63.7+/-4.7% to 24.2+/-1.8% (P< 0.0001). 5-hydroxydeanoate (100 microM) reduced the protection of diazoxide (46.8+/-2.7% cells hypercontracted, P< 0.0001 vs diazoxide alone). 5. Diazoxide caused no detectable change in flavoprotein autofluorescence (n=26 cells). 6. Our results suggest that mitochondrial depolarization and flavoprotein oxidation are not inevitable consequences of diazoxide application in intact cardiac myocytes, and that they are also not essential components of the mechanism by which it causes protection.
DOI Link: 10.1038/sj.bjp.0704289
ISSN: 0007-1188
Type: Journal Article
Appears in Collections:Published Articles, Dept. of Cell Physiology and Pharmacology

Files in This Item:
There are no files associated with this item.

Items in LRA are protected by copyright, with all rights reserved, unless otherwise indicated.