We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Effects of hydrogen peroxide on voltage-dependent K<sup>+</sup> currents in human cardiac fibroblasts through protein kinase pathways.
- Authors
Hyemi Bae; Donghee Lee; Young-Won Kim; Jeongyoon Choi; Hong Jun Lee; Sang-Wook Kim; Taeho Kim; Yun-Hee Noh; Jae-Hong Ko; Hyoweon Bang; Inja Lim
- 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+ (KCa) currents but not delayed rectifier K+ or transient outward K+ currents, all of which are VDKCs. H2O2- stimulated KCa currents were blocked by iberiotoxin (IbTX, a large conductance KCa blocker). The H2O2-stimulating effect on large-conductance KCa (BKCa) 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 BKCa currents. In contrast, KT5720 and H-89 (protein kinase A inhibitors) did not block the H2O2-stimulating effect on BKCa currents. Using RT-PCR and western blot analysis, three subtypes of KCa channels were detected in HCFs: BKCa channels, smallconductance KCa (SKCa) channels, and intermediate-conductance KCa (IKCa) 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 BKCa currents through the protein kinase G pathway but not the protein kinase A pathway, and is involved in cell injury through BKCa channels.
- Subjects
FIBROBLASTS; HYDROGEN peroxide; HEART fibrosis; PROTEIN kinases; CGMP-dependent protein kinase
- Publication
Korean Journal of Physiology & Pharmacology, 2016, Vol 20, Issue 3, p315
- ISSN
1226-4512
- Publication type
Article
- DOI
10.4196/kjpp.2016.20.3.315