Work

Carbon monoxide activates large-conductance calcium-activated potassium channels of human cardiac fibroblasts through various mechanisms

Year: 2021

Type: article

Abstract: Carbon monoxide (CO) is a cardioprotectant and potential cardiovascular therapeutic agent.Human cardiac fibroblasts (HCFs) are important determinants of myocardial structure and function.Large-conductance Ca 2+ -activated K + (BK) channel is a potential therapeutic target for cardiovascular disease.We investigated whether CO modulates BK channels and the signaling pathways in HCFs using whole-cell mode patch-clamp recordings.CO-releasing molecules (CORMs; CORM-2 and CORM-3) significantly increased the amplitudes of BK currents (IBK).The CO-induced stimulating effects on IBK were blocked by pre-treatment with specific nitric oxide synthase (NOS) blockers (L-N G -monomethyl arginine citrate and L-N G -nitroarginine methyl ester).8-bromo-cyclic GMP increased IBK.KT5823 (inhibits PKG) or ODQ (inhibits soluble guanylate cyclase) blocked the CO-stimulating effect on IBK.Moreover, 8-bromo-cyclic AMP also increased IBK, and pre-treatment with KT5720 (inhibits PKA) or SQ22536 (inhibits adenylate cyclase) blocked the CO effect.Pre-treatment with Nethylmaleimide (a thiol-alkylating reagent) also blocked the CO effect on IBK, and DLdithiothreitol (a reducing agent) reversed the CO effect.These data suggest that CO activates IBK through NO via the NOS and through the PKG, PKA, and S-nitrosylation pathways.

Source: Korean Journal of Physiology and Pharmacology

DOI: 10.4196/kjpp.2021.25.3.227

Authors: Hyemi Bae, Taeho Kim, Inja Lim

Institutions: Chung-Ang University, Chung-Ang University Hospital

Language: English

Topic: Heme Oxygenase-1 and Carbon Monoxide

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: diamond

Funders: National Research Foundation, Ministry of Education, National Research Foundation of Korea