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SHR Neuro Krebs Kardio Lipid Stoffw 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-Autor*innen der 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
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