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Oxygen-Glucose Deprivation and Reoxygenation as an In Vitro Ischemia-Reperfusion Injury Model for Studying Blood-Brain Barrier Dysfunction
Published on: May 7, 2015
Hypoxia and ischemia-reperfusion: a BiK contribution?
Jean-Yves Tano1, Maik Gollasch2
1Experimental and Clinical Research Center (a Joint Institution Between the Charité University Medicine and Max Delbrück Center for Molecular Medicine), Berlin-Buch, Germany; and Nephrology/Intensive Care Section, Charité Campus Virchow, Berlin, Germany jean-yves.tano@charite.de.
Insights
Large-conductance calcium-activated potassium channels (BK) show protective effects against ischemia-reperfusion injury. Their role in hypoxia and cardiovascular disease is increasingly recognized.
Area of Science:
- Cardiovascular Science
- Neuroscience
- Molecular Biology
Background:
- Cardiovascular diseases, particularly atherosclerosis, are leading causes of death globally.
- Ischemic injuries in the brain and heart result from excess calcium influx.
- Large-conductance calcium-activated potassium channels (BK) are potential targets for mitigating ischemic damage.
Purpose of the Study:
- To review the emerging role of BK channels in hypoxia and ischemia-reperfusion injury.
- To highlight the protective functions of mitochondrial BK channels (mitoBK).
- To discuss the sensitivity of BK channels to hypoxia via specific motifs.
Main Methods:
- Literature review of recent developments in BK channel research.
- Analysis of in vitro and animal models of ischemia-reperfusion injury.
- Examination of the molecular mechanisms underlying BK channel function in hypoxia.
Main Results:
- Mitochondrial BK channels (mitoBK) demonstrate a protective role against ischemia-reperfusion injury.
- The alpha-subunit of BK channels exhibits hypoxia sensitivity, mediated by the STREX motif.
- Tissue-specific sensitivity to hypoxia is conferred by alternative splicing.
Conclusions:
- BK channels, especially mitoBK, are crucial in protecting against ischemic events.
- Understanding BK channel regulation by hypoxia is vital for developing new therapeutic strategies.
- Further research is needed to elucidate the precise mechanisms of BK channel-mediated protection.
Abstract:
Over the last decades, cardiovascular disease has become the primary cause of death in the Western world, and this trend is expanding throughout the world. In particular, atherosclerosis and the subsequent vessel obliterations are the primary cause of ischemic disease (stroke and coronary heart disease). Excess calcium influx into the cells is one of the major pathophysiological mechanisms important for ischemic injury in the brain and heart in humans. The large-conductance calcium-activated K(+) channels (BK) are thus interesting candidates to protect against excess calcium influx and the events leading to ischemic injury. Indeed, the mitochondrial BK channels (mitoBK) have recently been shown to play a protective function against ischemia-reperfusion injury both in vitro and in animal models, although the exact mechanism of this protection is still under scrutiny. In addition, in both the plasma membrane and mitochondrial BK channel, the α-subunit itself is sensitive to hypoxia. This sensitivity is tissue specific and conferred by a highly conserved motif within an alternatively spliced cysteine-rich insert (STREX) in the intracellular C terminus of the channel. This review describes recent developments of the increasing relevance of BK channels in hypoxia and ischemia-reperfusion injury.
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