Increased calcium vulnerability of senescent cardiac mitochondria

Protective role for a mitochondrial potassium channel opener

Arshad Jahangir, Cevher Ozcan, Ekhson L. Holmuhamedov, Andre Terzic

Research output: Contribution to journalArticle

73 Citations (Scopus)

Abstract

In senescence, endogenous mechanisms of cardioprotection are apparently attenuated resulting in increased vulnerability to ischemia-reperfusion. In particular, mitochondria, which are essential in maintaining cardiac energetic and ionic homeostasis, are susceptible to Ca2+ overload, a component of metabolic injury. However, effective means of protecting senescent mitochondria are lacking. Here, mitochondrial function and structure were assessed using ion-selective mini-electrodes, high-performance liquid chromatography and electron microscopy. Aging decreased ADP-induced oxygen consumption and prolonged the time associated with ADP to ATP conversion, which manifested as a reduced rate of oxidative phosphorylation. Aging also reduced mitochondrial Ca2+ handling, and increased Ca2+-induced mitochondrial damage. Diazoxide, a potassium channel opener, reduced Ca2+ loading and protected the functional and structural integrity of senescent mitochondria from Ca2+-induced injury. In this way, the present study identifies the potential usefulness for pharmacotherapy in protecting vulnerable senescent mitochondria from conditions of Ca2+ overload, such as ischemia-reperfusion.

Original languageEnglish (US)
Pages (from-to)1073-1086
Number of pages14
JournalMechanisms of Ageing and Development
Volume122
Issue number10
DOIs
StatePublished - Jul 31 2001

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Mitochondria
Potassium Channels
Calcium
Adenosine Diphosphate
Reperfusion
Ischemia
Aging of materials
Ion-Selective Electrodes
Diazoxide
Drug therapy
Oxidative Phosphorylation
Wounds and Injuries
High performance liquid chromatography
Structural integrity
Oxygen Consumption
Electron microscopy
Electron Microscopy
Homeostasis
Adenosine Triphosphate
High Pressure Liquid Chromatography

Keywords

  • Aging
  • Calcium
  • Cardioprotection
  • Diazoxide
  • K-ATP channel
  • Senescence

ASJC Scopus subject areas

  • Aging
  • Biochemistry
  • Developmental Biology
  • Developmental Neuroscience

Cite this

Increased calcium vulnerability of senescent cardiac mitochondria : Protective role for a mitochondrial potassium channel opener. / Jahangir, Arshad; Ozcan, Cevher; Holmuhamedov, Ekhson L.; Terzic, Andre.

In: Mechanisms of Ageing and Development, Vol. 122, No. 10, 31.07.2001, p. 1073-1086.

Research output: Contribution to journalArticle

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