Related Experiment Video
Updated: May 12, 2026

A Flow Cytometry-based Assay for Measuring Mitochondrial Membrane Potential in Cardiac Myocytes After Hypoxia/Reoxygenation
Published on: July 13, 2018
Selective pharmacological agents implicate mitochondrial but not sarcolemmal K(ATP) channels in ischemic
T Sato1, N Sasaki, J Seharaseyon
1Institute of Molecular Cardiobiology, Johns Hopkins University, Baltimore, Md, USA.
Background:
Pharmacological evidence has implicated ATP-sensitive K(+) (K(ATP)) channels as the effectors of cardioprotection, but the relative roles of mitochondrial (mitoK(ATP)) and sarcolemmal (surfaceK(ATP)) channels remain controversial.
Methods And Results:
We examined the effects of the K(ATP) channel blocker HMR1098 and the K(ATP) channel opener P-1075 on surfaceK(ATP) and mitoK(ATP) channels in rabbit ventricular myocytes. HMR1098 (30 micromol/L) inhibited the surfaceK(ATP) current activated by metabolic inhibition, whereas the drug did not blunt diazoxide (100 micromol/L)-induced flavoprotein oxidation, an index of mitoK(ATP) channel activity. P-1075 (30 micromol/L) did not increase flavoprotein oxidation but did elicit a robust surfaceK(ATP) current that was completely inhibited by HMR1098. These results indicate that HMR1098 selectively inhibits surfaceK(ATP) channels, whereas P-1075 selectively activates surface K(ATP) channels. In a cellular model of simulated ischemia, the mitoK(ATP) channel opener diazoxide (100 micromol/L), but not P-1075, blunted cellular injury. The cardioprotection afforded by diazoxide or by preconditioning was prevented by the mitoK(ATP) channel blocker 5-hydroxydecanoate (500 micromol/L) but not by the surfaceK(ATP) channel blocker HMR1098 (30 micromol/L).
Conclusions:
The cellular effects of mitochondria- or surface-selective agents provide further support for the emerging consensus that mitoK(ATP) channels rather than surfaceK(ATP) channels are the likely effectors of cardioprotection.
Related Concept Videos
Electron Transport Chain: Complex I and II
ROS generation is regulated and maintained at moderate levels necessary...
ATP Synthase: Mechanism
The Electron Transport Chain
Inhibitors of the electron transport chain
Rotenone, a widely used pesticide, prevents electron transfer from Fe-S cluster to ubiquinone or Q in...
Antiarrhythmic Drugs: Class I Agents as Sodium Channel Blockers
Class 1A Antiarrhythmic Drugs: These drugs work by moderately blocking sodium channels,...
Antiarrhythmic Drugs: Class III Agents as Potassium Channel Blockers
Heart Failure Drugs: Inotropic Agents

