KCNMA1 encoded cardiac BK channels afford protection against ischemia-reperfusion injury

Publikation: Bidrag til tidsskriftTidsskriftartikelfagfællebedømt

Standard

KCNMA1 encoded cardiac BK channels afford protection against ischemia-reperfusion injury. / Soltysinska, Ewa; Bentzen, Bo Hjorth; Barthmes, Maria; Hattel, Helle; Thrush, A Brianne; Harper, Mary-Ellen; Qvortrup, Klaus; Larsen, Filip J; Schiffer, Tomas A; Losa-Reyna, Jose; Straubinger, Julia; Kniess, Angelina; Thomsen, Morten Bækgaard; Brüggemann, Andrea; Fenske, Stefanie; Biel, Martin; Ruth, Peter; Wahl-Schott, Christian; Boushel, Robert Christopher; Olesen, Søren-Peter; Lukowski, Robert.

I: PLOS ONE, Bind 9, Nr. 7, e103402, 2014, s. 1-12.

Publikation: Bidrag til tidsskriftTidsskriftartikelfagfællebedømt

Harvard

Soltysinska, E, Bentzen, BH, Barthmes, M, Hattel, H, Thrush, AB, Harper, M-E, Qvortrup, K, Larsen, FJ, Schiffer, TA, Losa-Reyna, J, Straubinger, J, Kniess, A, Thomsen, MB, Brüggemann, A, Fenske, S, Biel, M, Ruth, P, Wahl-Schott, C, Boushel, RC, Olesen, S-P & Lukowski, R 2014, 'KCNMA1 encoded cardiac BK channels afford protection against ischemia-reperfusion injury', PLOS ONE, bind 9, nr. 7, e103402, s. 1-12. https://doi.org/10.1371/journal.pone.0103402

APA

Soltysinska, E., Bentzen, B. H., Barthmes, M., Hattel, H., Thrush, A. B., Harper, M-E., Qvortrup, K., Larsen, F. J., Schiffer, T. A., Losa-Reyna, J., Straubinger, J., Kniess, A., Thomsen, M. B., Brüggemann, A., Fenske, S., Biel, M., Ruth, P., Wahl-Schott, C., Boushel, R. C., ... Lukowski, R. (2014). KCNMA1 encoded cardiac BK channels afford protection against ischemia-reperfusion injury. PLOS ONE, 9(7), 1-12. [e103402]. https://doi.org/10.1371/journal.pone.0103402

Vancouver

Soltysinska E, Bentzen BH, Barthmes M, Hattel H, Thrush AB, Harper M-E o.a. KCNMA1 encoded cardiac BK channels afford protection against ischemia-reperfusion injury. PLOS ONE. 2014;9(7):1-12. e103402. https://doi.org/10.1371/journal.pone.0103402

Author

Soltysinska, Ewa ; Bentzen, Bo Hjorth ; Barthmes, Maria ; Hattel, Helle ; Thrush, A Brianne ; Harper, Mary-Ellen ; Qvortrup, Klaus ; Larsen, Filip J ; Schiffer, Tomas A ; Losa-Reyna, Jose ; Straubinger, Julia ; Kniess, Angelina ; Thomsen, Morten Bækgaard ; Brüggemann, Andrea ; Fenske, Stefanie ; Biel, Martin ; Ruth, Peter ; Wahl-Schott, Christian ; Boushel, Robert Christopher ; Olesen, Søren-Peter ; Lukowski, Robert. / KCNMA1 encoded cardiac BK channels afford protection against ischemia-reperfusion injury. I: PLOS ONE. 2014 ; Bind 9, Nr. 7. s. 1-12.

Bibtex

@article{d9398214b9634cf889b53132c526f8eb,
title = "KCNMA1 encoded cardiac BK channels afford protection against ischemia-reperfusion injury",
abstract = "Mitochondrial potassium channels have been implicated in myocardial protection mediated through pre-/postconditioning. Compounds that open the Ca2+- and voltage-activated potassium channel of big-conductance (BK) have a pre-conditioning-like effect on survival of cardiomyocytes after ischemia/reperfusion injury. Recently, mitochondrial BK channels (mitoBKs) in cardiomyocytes were implicated as infarct-limiting factors that derive directly from the KCNMA1 gene encoding for canonical BKs usually present at the plasma membrane of cells. However, some studies challenged these cardio-protective roles of mitoBKs. Herein, we present electrophysiological evidence for paxilline- and NS11021-sensitive BK-mediated currents of 190 pS conductance in mitoplasts from wild-type but not BK-/- cardiomyocytes. Transmission electron microscopy of BK-/- ventricular muscles fibres showed normal ultra-structures and matrix dimension, but oxidative phosphorylation capacities at normoxia and upon re-oxygenation after anoxia were significantly attenuated in BK-/- permeabilized cardiomyocytes. In the absence of BK, post-anoxic reactive oxygen species (ROS) production from cardiomyocyte mitochondria was elevated indicating that mitoBK fine-tune the oxidative state at hypoxia and re-oxygenation. Because ROS and the capacity of the myocardium for oxidative metabolism are important determinants of cellular survival, we tested BK-/- hearts for their response in an ex-vivo model of ischemia/reperfusion (I/R) injury. Infarct areas, coronary flow and heart rates were not different between wild-type and BK-/- hearts upon I/R injury in the absence of ischemic pre-conditioning (IP), but differed upon IP. While the area of infarction comprised 28±3% of the area at risk in wild-type, it was increased to 58±5% in BK-/- hearts suggesting that BK mediates the beneficial effects of IP. These findings suggest that cardiac BK channels are important for proper oxidative energy supply of cardiomyocytes at normoxia and upon re-oxygenation after prolonged anoxia and that IP might indeed favor survival of the myocardium upon I/R injury in a BK-dependent mode stemming from both mitochondrial post-anoxic ROS modulation and non-mitochondrial localizations.",
author = "Ewa Soltysinska and Bentzen, {Bo Hjorth} and Maria Barthmes and Helle Hattel and Thrush, {A Brianne} and Mary-Ellen Harper and Klaus Qvortrup and Larsen, {Filip J} and Schiffer, {Tomas A} and Jose Losa-Reyna and Julia Straubinger and Angelina Kniess and Thomsen, {Morten B{\ae}kgaard} and Andrea Br{\"u}ggemann and Stefanie Fenske and Martin Biel and Peter Ruth and Christian Wahl-Schott and Boushel, {Robert Christopher} and S{\o}ren-Peter Olesen and Robert Lukowski",
year = "2014",
doi = "10.1371/journal.pone.0103402",
language = "English",
volume = "9",
pages = "1--12",
journal = "PLoS ONE",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "7",

}

RIS

TY - JOUR

T1 - KCNMA1 encoded cardiac BK channels afford protection against ischemia-reperfusion injury

AU - Soltysinska, Ewa

AU - Bentzen, Bo Hjorth

AU - Barthmes, Maria

AU - Hattel, Helle

AU - Thrush, A Brianne

AU - Harper, Mary-Ellen

AU - Qvortrup, Klaus

AU - Larsen, Filip J

AU - Schiffer, Tomas A

AU - Losa-Reyna, Jose

AU - Straubinger, Julia

AU - Kniess, Angelina

AU - Thomsen, Morten Bækgaard

AU - Brüggemann, Andrea

AU - Fenske, Stefanie

AU - Biel, Martin

AU - Ruth, Peter

AU - Wahl-Schott, Christian

AU - Boushel, Robert Christopher

AU - Olesen, Søren-Peter

AU - Lukowski, Robert

PY - 2014

Y1 - 2014

N2 - Mitochondrial potassium channels have been implicated in myocardial protection mediated through pre-/postconditioning. Compounds that open the Ca2+- and voltage-activated potassium channel of big-conductance (BK) have a pre-conditioning-like effect on survival of cardiomyocytes after ischemia/reperfusion injury. Recently, mitochondrial BK channels (mitoBKs) in cardiomyocytes were implicated as infarct-limiting factors that derive directly from the KCNMA1 gene encoding for canonical BKs usually present at the plasma membrane of cells. However, some studies challenged these cardio-protective roles of mitoBKs. Herein, we present electrophysiological evidence for paxilline- and NS11021-sensitive BK-mediated currents of 190 pS conductance in mitoplasts from wild-type but not BK-/- cardiomyocytes. Transmission electron microscopy of BK-/- ventricular muscles fibres showed normal ultra-structures and matrix dimension, but oxidative phosphorylation capacities at normoxia and upon re-oxygenation after anoxia were significantly attenuated in BK-/- permeabilized cardiomyocytes. In the absence of BK, post-anoxic reactive oxygen species (ROS) production from cardiomyocyte mitochondria was elevated indicating that mitoBK fine-tune the oxidative state at hypoxia and re-oxygenation. Because ROS and the capacity of the myocardium for oxidative metabolism are important determinants of cellular survival, we tested BK-/- hearts for their response in an ex-vivo model of ischemia/reperfusion (I/R) injury. Infarct areas, coronary flow and heart rates were not different between wild-type and BK-/- hearts upon I/R injury in the absence of ischemic pre-conditioning (IP), but differed upon IP. While the area of infarction comprised 28±3% of the area at risk in wild-type, it was increased to 58±5% in BK-/- hearts suggesting that BK mediates the beneficial effects of IP. These findings suggest that cardiac BK channels are important for proper oxidative energy supply of cardiomyocytes at normoxia and upon re-oxygenation after prolonged anoxia and that IP might indeed favor survival of the myocardium upon I/R injury in a BK-dependent mode stemming from both mitochondrial post-anoxic ROS modulation and non-mitochondrial localizations.

AB - Mitochondrial potassium channels have been implicated in myocardial protection mediated through pre-/postconditioning. Compounds that open the Ca2+- and voltage-activated potassium channel of big-conductance (BK) have a pre-conditioning-like effect on survival of cardiomyocytes after ischemia/reperfusion injury. Recently, mitochondrial BK channels (mitoBKs) in cardiomyocytes were implicated as infarct-limiting factors that derive directly from the KCNMA1 gene encoding for canonical BKs usually present at the plasma membrane of cells. However, some studies challenged these cardio-protective roles of mitoBKs. Herein, we present electrophysiological evidence for paxilline- and NS11021-sensitive BK-mediated currents of 190 pS conductance in mitoplasts from wild-type but not BK-/- cardiomyocytes. Transmission electron microscopy of BK-/- ventricular muscles fibres showed normal ultra-structures and matrix dimension, but oxidative phosphorylation capacities at normoxia and upon re-oxygenation after anoxia were significantly attenuated in BK-/- permeabilized cardiomyocytes. In the absence of BK, post-anoxic reactive oxygen species (ROS) production from cardiomyocyte mitochondria was elevated indicating that mitoBK fine-tune the oxidative state at hypoxia and re-oxygenation. Because ROS and the capacity of the myocardium for oxidative metabolism are important determinants of cellular survival, we tested BK-/- hearts for their response in an ex-vivo model of ischemia/reperfusion (I/R) injury. Infarct areas, coronary flow and heart rates were not different between wild-type and BK-/- hearts upon I/R injury in the absence of ischemic pre-conditioning (IP), but differed upon IP. While the area of infarction comprised 28±3% of the area at risk in wild-type, it was increased to 58±5% in BK-/- hearts suggesting that BK mediates the beneficial effects of IP. These findings suggest that cardiac BK channels are important for proper oxidative energy supply of cardiomyocytes at normoxia and upon re-oxygenation after prolonged anoxia and that IP might indeed favor survival of the myocardium upon I/R injury in a BK-dependent mode stemming from both mitochondrial post-anoxic ROS modulation and non-mitochondrial localizations.

U2 - 10.1371/journal.pone.0103402

DO - 10.1371/journal.pone.0103402

M3 - Journal article

C2 - 25072914

VL - 9

SP - 1

EP - 12

JO - PLoS ONE

JF - PLoS ONE

SN - 1932-6203

IS - 7

M1 - e103402

ER -

ID: 124262577