Global and conditional deletion of Slick K+ channels in cardiac myofibroblasts reduced fibrosis and preserved left ventricular function following ischemia/reperfusion injury in mice.
Does Slick K+ channel deletion prevent adverse cardiac remodeling, fibrosis, and dysfunction in post-infarction hearts?
Deletion of Slick K+ channels in cardiac myofibroblasts mitigates maladaptive fibrotic remodeling and functional decline after myocardial infarction.
Resident cardiac fibroblast (RCF)-derived cardiac myofibroblasts (CMF) 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 following ischemia/reperfusion injury. This cardioprotection was associated with diminished CMF activation and proliferation, reduced inflammation, and improved CM survival post-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.
Yang et al. (Tue,) conducted a other in Myocardial infarction and cardiac fibrosis. Slick (Slo2.1) knockout vs. Wild-type controls was evaluated on Cardiac fibrosis and left ventricular function. Global and conditional deletion of Slick K+ channels in cardiac myofibroblasts reduced fibrosis and preserved left ventricular function following ischemia/reperfusion injury in mice.