Carbon Monoxide Activates Large-conductance Calcium-activated Potassium Channels of Human Cardiac Fibroblasts Through Various Mechanisms

Overview

Journal Korean J Physiol Pharmacol

Specialty Pharmacology

Date 2021 Apr 16

PMID 33859063

Citations 3

Authors

Hyemi Bae

Taeho Kim

Inja Lim

Affiliations

Soon will be listed here.

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-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 (). The CO-induced stimulating effects on were blocked by pre-treatment with specific nitric oxide synthase (NOS) blockers (L-N-monomethyl arginine citrate and L-N-nitroarginine methyl ester). 8-bromo-cyclic GMP increased . KT5823 (inhibits PKG) or ODQ (inhibits soluble guanylate cyclase) blocked the CO-stimulating effect on . Moreover, 8-bromo-cyclic AMP also increased , 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 , and DLdithiothreitol (a reducing agent) reversed the CO effect. These data suggest that CO activates through NO the NOS and through the PKG, PKA, and -nitrosylation pathways.

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