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Journal article
Inhibition of BKCa channels protects neonatal hearts against myocardial ischemia and reperfusion injury
Cell death discovery, v 8(1), 175
07 Apr 2022
PMID: 35393410
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
BKCa channels are large-conductance calcium and voltage-activated potassium channels that are heterogeneously expressed in a wide array of cells. Activation of BKCa channels present in mitochondria of adult ventricular cardiomyocytes is implicated in cardioprotection against ischemia-reperfusion (IR) injury. However, the BKCa channel's activity has never been detected in the plasma membrane of adult ventricular cardiomyocytes. In this study, we report the presence of the BKCa channel in the plasma membrane and mitochondria of neonatal murine and rodent cardiomyocytes, which protects the heart on inhibition but not activation. Furthermore, K+ currents measured in neonatal cardiomyocyte (NCM) was sensitive to iberiotoxin (IbTx), suggesting the presence of BKCa channels in the plasma membrane. Neonatal hearts subjected to IR when post-conditioned with NS1619 during reoxygenation increased the myocardial infarction whereas IbTx reduced the infarct size. In agreement, isolated NCM also presented increased apoptosis on treatment with NS1619 during hypoxia and reoxygenation, whereas IbTx reduced TUNEL-positive cells. In NCMs, activation of BKCa channels increased the intracellular reactive oxygen species post HR injury. Electrophysiological characterization of NCMs indicated that NS1619 increased the beat period, field, and action potential duration, and decreased the conduction velocity and spike amplitude. In contrast, IbTx had no impact on the electrophysiological properties of NCMs. Taken together, our data established that inhibition of plasma membrane BKCa channels in the NCM protects neonatal heart/cardiomyocytes from IR injury. Furthermore, the functional disparity observed towards the cardioprotective activity of BKCa channels in adults compared to neonatal heart could be attributed to their differential localization.
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Details
- Title
- Inhibition of BKCa channels protects neonatal hearts against myocardial ischemia and reperfusion injury
- Creators
- Shridhar Sanghvi - The Ohio State University Wexner Medical CenterKalina Szteyn - The Ohio State University Wexner Medical CenterDevasena Ponnalagu - Ohio State Univ, Wexner Med Ctr, Dept Physiol & Cell Biol, Columbus, OH 43210 USADivya Sridharan - The Ohio State University Wexner Medical CenterAlexender Lam - Drexel UniversityInderjot Hansra - The Ohio State University Wexner Medical CenterAnkur Chaudhury - Drexel UniversityUddalak Majumdar - Nationwide Children's HospitalAndrew R. Kohut - Drexel Univ, Coll Med, Dept Internal Med, Philadelphia, PA 19104 USAShubha Gururaja Rao - Ohio Northern Univ, Raabe Coll Pharm, Dept Pharmaceut & Biomed Sci, Ada, OH USAMahmood Khan - The Ohio State University Wexner Medical CenterVidu Garg - Nationwide Children's HospitalHarpreet Singh (Corresponding Author) - Ohio State Univ, Wexner Med Ctr, Dept Physiol & Cell Biol, Columbus, OH 43210 USA
- Publication Details
- Cell death discovery, v 8(1), 175
- Publisher
- Springer Nature
- Number of pages
- 13
- Grant note
- 11SDG7230059 / AHA Scientist Development grant; American Heart Association W. W. Smith Charitable Trust 11SDG7230059; 20CDA35310714 / American Heart Association (AHA); American Heart Association R01- HL133050; R01-HL157453 / National Institutes of Health (NIH); United States Department of Health & Human Services; National Institutes of Health (NIH) - USA Ohio State University Department of Physiology and Cell Biology Margaret T. Nishikawara Merit Scholarship Endowment in Physiology 20CDA35310714 / American Heart Association (AHA) Career Development Award; American Heart Association
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- College of Medicine
- Web of Science ID
- WOS:000779755500002
- Scopus ID
- 2-s2.0-85128197346
- Other Identifier
- 991021861173904721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Cell Biology