Mitochondrial membrane fluidity, potential, and calcium transients in the myocardium from acute diabetic ratsThis paper is one of a selection of papers published in this Special Issue, entitled The Cellular and Molecular Basis of Cardiovascular Dysfunction, Dhalla 70th Birthday Tribute.

Abstract

In this study, we report for the first time concurrent measurements of membrane potential and dynamics and respiratory chain activities in rat heart mitochondria, as well as calcium transients in the hearts of rats in an early phase of streptozotocin diabetes, not yet accompanied with diabetes-induced complications. Quantitative relationships among these variables were assessed. The mitochondria from diabetic rats exhibited decreased fluorescence anisotropy values of diphenylhexatriene. This indicates that hydrophobic core of the membranes was more fluid compared with controls (p<0.05). We discuss the changes in fluidity as having been associated with augmented energy transduction through the diabetic membranes. Reduced ratio of JC-1 fluorescence (aggregates to monomers) in the mitochondria from diabetic hearts reflected descendent transmembrane potential. A significant negative association between membrane fluidity and potential in the diabetic group was found (p<0.05; r=0.67). Further, we observed an increase in calcium transient amplitude (CTA) in the diabetic cardiomyocytes (p=0.048). We conclude that some of the calcium-induced regulatory events that dictate fuel selection and capacity for ATP production in diabetic heart occur at the membrane level. Our findings offer new insight into acute diabetes-induced changes in cardiac mitochondria.

Methylene blue improves mitochondrial respiration and decreases oxidative stress in a substrate-dependent manner in diabetic rat hearts

“…Nevertheless, we admit as important limitation of our study the fact that we did not measure the mitochondrial membrane potential, especially since Waczulikova et al demonstrated a slight decline of the membrane potential concomitant with an increased membrane fluidity in acute (i.e., 8 days) streptozotocin-induced diabetic rat hearts (Waczulikova et al 2007).…”

“…Coronary heart disease (CHD) is the leading cause of mortality due to myocardial infarction and of morbidity due to heart failure. In the past decades, mitochondrial dysfunction have emerged in both conditions central effectors of the pathomechanisms underlying both acute and chronic cardiac diseases as well as potential therapeutic targets (Bulluck et al 2016;Waczulikova et al 2007). Diabetes mellitus (DM), acknowledged as the pandemy of our century, is responsible for the diabetic cardiomyopathy, defined as the association of left ventricular hypertrophy/remodeling with diastolic dysfunction that precedes the development of systolic dysfunction and may progress to heart failure (Duicu et al 2015a).…”

Dual influence of spontaneous hypertension on membrane properties and ATP production in heart and kidney mitochondria in rat: effect of captopril and nifedipine, adaptation and dysadaptation

“…A high degree of fluorescence anisotropy indicates a high degree of structural order or lower membrane fluidity (Shinitzky 1984). For more details see Waczulíková et al (2000Waczulíková et al ( , 2007 and Ferko et al (2006b).…”

Mitochondrial function in heart and kidney of spontaneously hypertensive rats: influence of captopril treatment

“…The method for estimation of the mitochondrial Mg 2+ -ATPase activity and determination of the proper season for carrying out the experiment were described in our earlier paper Mujkošová et al (2008). Fluidity of mitochondrial membranes was estimated according to Waczulíková et al (2007), mitochondria oxygen consumption (QO 2 ) and oxidative phosphorylation according to Ziegelhöffer et al (2009) and protein concentration in the mitochondrial fraction according to Lowry et al (1953). If not indicated differently in the text, all organic chemicals were purchased from Sigma-Aldrich and the inorganic ones from Merck or Lachema (Czech Republic) and were of analytical grade.…”

“…Fluidization of heart mito- chondrial membranes may be caused by various factors. Nevertheless, it can´t be excluded that an increase in the amount of trans-membrane substrate and energy transition pores associated with a decrease in mitochondrial membrane potential (Waczulíková et al 2007;Ferko et al 2008) is also participating in this phenomenon. Such an increase in substrate and energy transition pores formation in mitochondrial membranes is a feature common for diabetes as well as for hypertension and represents a protective process triggered by strong calcium signaling (Ziegelhöffer et al 2009).…”