Relationship between mitochondrial matrix volume and cellular volume in response to stress and the role of atp-sensitive potassium channel

Melissa M. Anastacio, Evelyn M. Kanter, Carol M. Makepeace, Angela D. Keith, Haixia Zhang, Richard B. Schuessler, Colin G. Nichols, Jennifer Lawton

Research output: Contribution to journalArticle

Abstract

BACKGROUND - Cardiac myocytes demonstrate significant swelling and associated reduced contractility in response to stress that is prevented by the ATP-sensitive potassium channel opener, diazoxide (DZX) via an unknown mechanism. One proposed mechanism of cardioprotection is mitochondrial matrix swelling. To establish the relationship between mitochondrial and cellular volume during stress, this study examined the effect of DZX on mitochondrial volume. METHODS AND RESULTS - Isolated mouse mitochondria were exposed to the following solutions: Tyrode, isolation buffer, cardioplegia (CPG) ±DZX±ATP-sensitive potassium channel inhibitor, 5-hydroxydecanoate, and metabolic inhibition (MI)±DZX±5- hydroxydecanoate. Mitochondrial volume was measured. DZX resulted in significant mitochondrial swelling (P<0.0001 versus Tyrode). MI and CPG resulted in significant mitochondrial swelling compared with baseline volume. The addition of DZX did not alter the response of mitochondrial volume to CPG (P=0.912) but increased swelling in response to MI (P=0.036). The addition of 5-hydroxydecanoate to MI+DZX or CPG+DZX significantly reduced mitochondrial swelling (P<0.003 MI+DZX versus MI+DZX+5HD; P<0.001 CPG+DZX versus CPG+DZX+5HD). CONCLUSIONS - Both cellular and mitochondrial volume increased during exposure to MI and CPG. DZX did not alter mitochondrial volume during CPG; however, it was associated with an increase in mitochondrial volume during MI. 5-Hydroxydecanoate reduced mitochondrial volume during exposure to both stresses with DZX, supporting a role for a mitochondrial ATP-sensitive potassium channel in the mechanism of cardioprotection by DZX.

Original languageEnglish (US)
JournalCirculation
Volume128
Issue numberSUPPL.1
DOIs
StatePublished - Sep 10 2013
Externally publishedYes

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Mitochondrial Size
Diazoxide
Potassium Channels
Induced Heart Arrest
Mitochondrial Swelling
KATP Channels
Cardiac Myocytes

Keywords

  • Cardioplegia
  • Myocardial ischemia
  • Myocardial stunning
  • Myocytes cardiac
  • Potassium channels

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Relationship between mitochondrial matrix volume and cellular volume in response to stress and the role of atp-sensitive potassium channel. / Anastacio, Melissa M.; Kanter, Evelyn M.; Makepeace, Carol M.; Keith, Angela D.; Zhang, Haixia; Schuessler, Richard B.; Nichols, Colin G.; Lawton, Jennifer.

In: Circulation, Vol. 128, No. SUPPL.1, 10.09.2013.

Research output: Contribution to journalArticle

Anastacio, Melissa M. ; Kanter, Evelyn M. ; Makepeace, Carol M. ; Keith, Angela D. ; Zhang, Haixia ; Schuessler, Richard B. ; Nichols, Colin G. ; Lawton, Jennifer. / Relationship between mitochondrial matrix volume and cellular volume in response to stress and the role of atp-sensitive potassium channel. In: Circulation. 2013 ; Vol. 128, No. SUPPL.1.
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AU - Anastacio, Melissa M.

AU - Kanter, Evelyn M.

AU - Makepeace, Carol M.

AU - Keith, Angela D.

AU - Zhang, Haixia

AU - Schuessler, Richard B.

AU - Nichols, Colin G.

AU - Lawton, Jennifer

PY - 2013/9/10

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N2 - BACKGROUND - Cardiac myocytes demonstrate significant swelling and associated reduced contractility in response to stress that is prevented by the ATP-sensitive potassium channel opener, diazoxide (DZX) via an unknown mechanism. One proposed mechanism of cardioprotection is mitochondrial matrix swelling. To establish the relationship between mitochondrial and cellular volume during stress, this study examined the effect of DZX on mitochondrial volume. METHODS AND RESULTS - Isolated mouse mitochondria were exposed to the following solutions: Tyrode, isolation buffer, cardioplegia (CPG) ±DZX±ATP-sensitive potassium channel inhibitor, 5-hydroxydecanoate, and metabolic inhibition (MI)±DZX±5- hydroxydecanoate. Mitochondrial volume was measured. DZX resulted in significant mitochondrial swelling (P<0.0001 versus Tyrode). MI and CPG resulted in significant mitochondrial swelling compared with baseline volume. The addition of DZX did not alter the response of mitochondrial volume to CPG (P=0.912) but increased swelling in response to MI (P=0.036). The addition of 5-hydroxydecanoate to MI+DZX or CPG+DZX significantly reduced mitochondrial swelling (P<0.003 MI+DZX versus MI+DZX+5HD; P<0.001 CPG+DZX versus CPG+DZX+5HD). CONCLUSIONS - Both cellular and mitochondrial volume increased during exposure to MI and CPG. DZX did not alter mitochondrial volume during CPG; however, it was associated with an increase in mitochondrial volume during MI. 5-Hydroxydecanoate reduced mitochondrial volume during exposure to both stresses with DZX, supporting a role for a mitochondrial ATP-sensitive potassium channel in the mechanism of cardioprotection by DZX.

AB - BACKGROUND - Cardiac myocytes demonstrate significant swelling and associated reduced contractility in response to stress that is prevented by the ATP-sensitive potassium channel opener, diazoxide (DZX) via an unknown mechanism. One proposed mechanism of cardioprotection is mitochondrial matrix swelling. To establish the relationship between mitochondrial and cellular volume during stress, this study examined the effect of DZX on mitochondrial volume. METHODS AND RESULTS - Isolated mouse mitochondria were exposed to the following solutions: Tyrode, isolation buffer, cardioplegia (CPG) ±DZX±ATP-sensitive potassium channel inhibitor, 5-hydroxydecanoate, and metabolic inhibition (MI)±DZX±5- hydroxydecanoate. Mitochondrial volume was measured. DZX resulted in significant mitochondrial swelling (P<0.0001 versus Tyrode). MI and CPG resulted in significant mitochondrial swelling compared with baseline volume. The addition of DZX did not alter the response of mitochondrial volume to CPG (P=0.912) but increased swelling in response to MI (P=0.036). The addition of 5-hydroxydecanoate to MI+DZX or CPG+DZX significantly reduced mitochondrial swelling (P<0.003 MI+DZX versus MI+DZX+5HD; P<0.001 CPG+DZX versus CPG+DZX+5HD). CONCLUSIONS - Both cellular and mitochondrial volume increased during exposure to MI and CPG. DZX did not alter mitochondrial volume during CPG; however, it was associated with an increase in mitochondrial volume during MI. 5-Hydroxydecanoate reduced mitochondrial volume during exposure to both stresses with DZX, supporting a role for a mitochondrial ATP-sensitive potassium channel in the mechanism of cardioprotection by DZX.

KW - Cardioplegia

KW - Myocardial ischemia

KW - Myocardial stunning

KW - Myocytes cardiac

KW - Potassium channels

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