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"Faces" of the day:

Klara Konstanze Pohl

Federica Piani

Cara Lavinia Shirin Rech

Kathrin Eller

Christine Moissl-Eichinger

Dajie Marschik

Eleonore Fröhlich

Konstantin Adrian Klötzer

Florian Moik

Marco Eigenfeld

Mahmoud Abdellatif

Benjamin Gottschalk

Christian Diener

Peter Marschik

Simon Sedej

Sascha Ahyai

Roland Malli

Wolfgang Graier

Selected Publication:

SHR Neuro Cancer Cardio Lipid Metab Microb

Roslan, A; Paulus, K; Yang, J; Matt, L; Bischof, H; Längst, N; Schanz, S; Luczak, A; Cruz, Santos, M; Burgstaller, S; Skrabak, D; Bork, NI; Malli, R; Schmidtko, A; Gawaz, M; Nikolaev, VO; Ruth, P; Ehinger, R; Lukowski, R.
Slack K+ channels confer protection against myocardial ischaemia/reperfusion injury.
Cardiovasc Res. 2025; 121(1):174-189 Doi: 10.1093/cvr/cvae155
Web of Science PubMed FullText FullText_MUG

Co-authors Med Uni Graz: Bischof Helmut; Burgstaller Sandra; Malli Roland
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Abstract:: AIMS: Na+-activated Slack potassium (K+) channels are increasingly recognized as regulators of neuronal activity, yet little is known about their role in the cardiovascular system. Slack activity increases when intracellular Na+ concentration ([Na+]i) reaches pathophysiological levels. Elevated [Na+]i is a major determinant of the ischaemia and reperfusion (I/R)-induced myocardial injury; thus, we hypothesized that Slack plays a role under these conditions. METHODS AND RESULTS: K+ currents in cardiomyocytes (CMs) obtained from wildtype but not from global Slack knockout mice were sensitive to electrical inactivation of voltage-sensitive Na+ channels. Live-cell imaging demonstrated that K+ fluxes across the sarcolemma rely on Slack, while the depolarized resting membrane potential in Slack-deficient CMs led to excessive cytosolic Ca2+ accumulation and finally to hypoxia/reoxygenation-induced cell death. Cardiac damage in an in vivo model of I/R was exacerbated in global and CM-specific conditional Slack mutants and largely insensitive to mechanical conditioning manoeuvres. Finally, the protection conferred by mitochondrial ATP-sensitive K+ (mitoKATP) channels required functional Slack in CMs. CONCLUSION: Collectively, our study provides evidence for Slack's crucial involvement in the ion homeostasis of no or low O2-stressed CMs. Thereby, Slack activity opposes the I/R-induced fatal Ca2+-uptake to CMs supporting the cardioprotective signaling attributed to mitoKATP function.
Find related publications in this database (using NLM MeSH Indexing): Animals - administration & dosage; Myocardial Reperfusion Injury - metabolism, prevention & control, pathology, genetics; Myocytes, Cardiac - metabolism, pathology; Mice, Knockout - administration & dosage; Potassium Channels - metabolism, genetics, deficiency; Disease Models, Animal - administration & dosage; Mice, Inbred C57BL - administration & dosage; Potassium - metabolism; Muscle Proteins - genetics, metabolism, deficiency; Sarcolemma - metabolism; Cells, Cultured - administration & dosage; Male - administration & dosage; Mitochondria, Heart - metabolism, pathology; Calcium Signaling - administration & dosage; Myocardial Infarction - metabolism, pathology, prevention & control, genetics; Calcium - metabolism
Find related publications in this database (Keywords): Cardiomyocyte; Cardioprotection; Ischaemia/reperfusion; K+ biosensor; KCNT1; K(Na)1.1; Myocardial infarction; Slack; Slo2.2