Your browser doesn't support javascript.
loading
ABSTRACT
Human cardiac fibroblasts (HCFs) have various voltage-dependent K+ channels (VDKCs) that can induce apoptosis. Hydrogen peroxide (H2O2) modulates VDKCs and induces oxidative stress, which is the main contributor to cardiac injury and cardiac remodeling. We investigated whether H2O2 could modulate VDKCs in HCFs and induce cell injury through this process. In whole-cell mode patch-clamp recordings, application of H2O2 stimulated Ca2+-activated K+ (K(Ca)) currents but not delayed rectifier K+ or transient outward K+ currents, all of which are VDKCs. H2O2-stimulated K(Ca) currents were blocked by iberiotoxin (IbTX, a large conductance K(Ca) blocker). The H2O2-stimulating effect on large-conductance K(Ca) (BK(Ca)) currents was also blocked by KT5823 (a protein kinase G inhibitor) and 1 H-[1, 2, 4] oxadiazolo-[4, 3-a] quinoxalin-1-one (ODQ, a soluble guanylate cyclase inhibitor). In addition, 8-bromo-cyclic guanosine 3', 5'-monophosphate (8-Br-cGMP) stimulated BK(Ca) currents. In contrast, KT5720 and H-89 (protein kinase A inhibitors) did not block the H2O2-stimulating effect on BK(Ca) currents. Using RT-PCR and western blot analysis, three subtypes of K(Ca) channels were detected in HCFs: BK(Ca) channels, small-conductance K(Ca) (SK(Ca)) channels, and intermediate-conductance K(Ca) (IK(Ca)) channels. In the annexin V/propidium iodide assay, apoptotic changes in HCFs increased in response to H2O2, but IbTX decreased H2O2-induced apoptosis. These data suggest that among the VDKCs of HCFs, H2O2 only enhances BK(Ca) currents through the protein kinase G pathway but not the protein kinase A pathway, and is involved in cell injury through BK(Ca) channels.
Subject(s)
Key words
Full text: 1 Database: WPRIM Main subject: Phosphotransferases / Protein Kinases / Blotting, Western / Apoptosis / Cyclic GMP-Dependent Protein Kinases / Cyclic AMP-Dependent Protein Kinases / Oxidative Stress / Potassium Channels, Calcium-Activated / Fibroblasts / Guanosine Limits: Humans Language: En Journal: The Korean Journal of Physiology and Pharmacology Year: 2016 Document type: Article
Full text: 1 Database: WPRIM Main subject: Phosphotransferases / Protein Kinases / Blotting, Western / Apoptosis / Cyclic GMP-Dependent Protein Kinases / Cyclic AMP-Dependent Protein Kinases / Oxidative Stress / Potassium Channels, Calcium-Activated / Fibroblasts / Guanosine Limits: Humans Language: En Journal: The Korean Journal of Physiology and Pharmacology Year: 2016 Document type: Article