Abstract 13313: The Relationship Between Mitochondrial Matrix Volume and Cellular Volume In Response to Stress and the Role of the Adenosine Triphosphate Sensitive Potassium Channel
Objectives: In the presence of stress (hyperkalemic cardioplegia (CPG), hypoosmotic stress, or metabolic inhibition (MI)) cardiac myocytes demonstrate significant swelling and associated reduced contractility which is prevented by the adenosine triphosphate-sensitive potassium (KATP) channel opener, Diazoxide (DZX) via an unknown mechanism. Mitochondrial matrix volume comprises up to 35% of cellular volume and one proposed mechanism of cardioprotection by DZX is mitochondrial matrix swelling. To establish the relationship between mitochondrial and cellular volume during stress, we evaluated the effects of DZX and the KATP channel inhibitor, 5-hydroxydecanoate (5-HD), on mitochondrial volume.
Methods: Isolated mouse mitochondria were exposed to test solutions: Tyrode’s solution (Control), Tyrode’s + DZX, CPG, CPG + DZX, CPG + DZX + 5HD, MI, MI + DZX, and MI + DZX + 5HD. Mitochondrial matrix volume was measured as percent change in absorbance at 520nm using a spectrophotometer.
Results: DZX alone resulted in significant mitochondrial matrix swelling (p<0.0001 vs Tyrode’s). MI resulted in significant mitochondrial matrix swelling (p<0.0001 vs Tyrode’s) but CPG did not (Figure 1A-1B). The addition of DZX did not alter the response to CPG (p=0.912) but increased the swelling in response to MI (p=0.036).The addition of 5-HD to MI + DZX or CPG + DZX significantly reduced mitochondrial swelling (p<0.05) when compared to each stress with DZX alone.
Conclusions: Unlike the change in cellular volume following exposure to CPG, exposure of mitochondria to CPG did not result in a change in mitochondrial volume. Similar to observed changes in cellular volume following exposure to MI, mitochondrial exposure to MI caused an increase in matrix volume. 5HD reduced matrix volume during exposure to both stresses with DZX implicating a role for a mitochondrial KATP channel in matrix volume regulation and in DZX’s mechanism of cardioprotection.
- © 2012 by American Heart Association, Inc.