Protection Against Cardiac Injury by Small Ca^{2 +}-Sensitive K⁺ Channels Identified in Guinea Pig Cardiac Inner Mitochondrial Membrane

Authors

David F. Stowe, Marquette University
Ashish K. Gadicherla, Medical College of Wisconsin
Yifan Zhou, Medical College of WisconsinFollow
Mohammed Aldakkak, Medical College of Wisconsin
Qunli Cheng, Medical College of WisconsinFollow
Wai-Meng Kwok, Medical College of Wisconsin
Ming Tao Jiang, Medical College of Wisconsin
James S. Heisner, Medical College of Wisconsin
MeiYing Yang, Medical College of WisconsinFollow
Amadou K.S. Camara, Medical College of Wisconsin

Document Type

Article

Language

eng

Publication Date

2-2013

Publisher

Elsevier

Source Publication

Biochimica et Biophysica Acta (BBA) - Biomembranes

Source ISSN

0005-2736

Abstract

We tested if small conductance, Ca^{2 +}‐sensitive K⁺ channels (SK_Ca) precondition hearts against ischemia reperfusion (IR) injury by improving mitochondrial (m) bioenergetics, if O₂‐derived free radicals are required to initiate protection via SK_Ca channels, and, importantly, if SK_Ca channels are present in cardiac cell inner mitochondrial membrane (IMM). NADH and FAD, superoxide (O₂⁻), and m[Ca^{2 +}] were measured in guinea pig isolated hearts by fluorescence spectrophotometry. SK_Ca and IK_Ca channel opener DCEBIO (DCEB) was given for 10 min and ended 20 min before IR. Either TBAP, a dismutator of O₂⁻, NS8593, an antagonist of SK_Ca isoforms, or other K_Ca and K_ATP channel antagonists, were given before DCEB and before ischemia. DCEB treatment resulted in a 2-fold increase in LV pressure on reperfusion and a 2.5 fold decrease in infarct size vs. non-treated hearts associated with reduced O₂⁻ and m[Ca^{2 +}], and more normalized NADH and FAD during IR. Only NS8593 and TBAP antagonized protection by DCEB. Localization of SK_Ca channels to mitochondria and IMM was evidenced by a) identification of purified mSK_Ca protein by Western blotting, immuno-histochemical staining, confocal microscopy, and immuno-gold electron microscopy, b) 2-D gel electrophoresis and mass spectroscopy of IMM protein, c) [Ca^{2 +}]‐dependence of mSK_Ca channels in planar lipid bilayers, and d) matrix K⁺ influx induced by DCEB and blocked by SK_Ca antagonist UCL1684. This study shows that 1) SK_Ca channels are located and functional in IMM, 2) mSK_Ca channel opening by DCEB leads to protection that is O₂⁻dependent, and 3) protection by DCEB is evident beginning during ischemia.

Comments

Accepted version. Biochimica et Biophysica Acta (BBA) - Biomembranes, Vol. 1828, No. 2 (February 2013): 427-442. DOI. © 2013 Elsevier B.V. Used with permission.

Recommended Citation

Stowe, David F.; Gadicherla, Ashish K.; Zhou, Yifan; Aldakkak, Mohammed; Cheng, Qunli; Kwok, Wai-Meng; Jiang, Ming Tao; Heisner, James S.; Yang, MeiYing; and Camara, Amadou K.S., "Protection Against Cardiac Injury by Small Ca^{2 +}-Sensitive K⁺ Channels Identified in Guinea Pig Cardiac Inner Mitochondrial Membrane" (2013). Biomedical Engineering Faculty Research and Publications. 545.
https://epublications.marquette.edu/bioengin_fac/545