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Slick K+ channels contribute to cardiac remodeling, fibrosis, and dysfunction in postinfarction hearts
Jiaqi Yang, Lin Zhu, David Spähn, Melanie Cruz Santos, Sophia Schanz, Selina Maier, Lena Birkenfeld, Helmut Bischof, Anna Roslan, Nina Wettschureck, Oliver Borst, Lucas Matt, Robert Lukowski
Jiaqi Yang, Lin Zhu, David Spähn, Melanie Cruz Santos, Sophia Schanz, Selina Maier, Lena Birkenfeld, Helmut Bischof, Anna Roslan, Nina Wettschureck, Oliver Borst, Lucas Matt, Robert Lukowski
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Research Article Cardiology Cell biology

Slick K+ channels contribute to cardiac remodeling, fibrosis, and dysfunction in postinfarction hearts

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Abstract

Resident cardiac fibroblast–derived (RCF-derived) cardiac myofibroblasts (CMFs) contribute to myocardial repair but also drive adverse ventricular remodeling and contractile dysfunction after myocardial infarction (MI). The sodium-activated potassium channel Slick (Slo2.1) has been described in cardiomyocyte (CM) mitochondria; however, transcriptomic analyses indicate higher Slick expression in RCFs/CMFs. Here, we investigated the role of Slick in cardiac fibroblast function and post-MI remodeling. Using live-cell imaging and whole-cell patch-clamp recordings, we found that plasma membrane Slick channels in RCFs and CMFs regulated potassium (K+) efflux and modulated store-operated calcium entry (SOCE), particularly in CMFs. Global Slick KO and conditional CMF-specific KO hearts exhibited reduced fibrosis and preserved left ventricular function after ischemia/reperfusion injury. This cardioprotection was associated with diminished CMF activation and proliferation, reduced inflammation, and improved CM survival after MI. Collectively, these findings identify fibroblast Slick channels as regulators of SOCE-dependent fibrogenesis and demonstrate that their deletion mitigates maladaptive remodeling and functional decline after MI.

Authors

Jiaqi Yang, Lin Zhu, David Spähn, Melanie Cruz Santos, Sophia Schanz, Selina Maier, Lena Birkenfeld, Helmut Bischof, Anna Roslan, Nina Wettschureck, Oliver Borst, Lucas Matt, Robert Lukowski

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Usage data is cumulative from March 2026 through July 2026.

Usage JCI PMC
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PDF 252 0
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Citation downloads 192 0
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