Journal article
L-type Ca2+ channel facilitation mediated by H2O2-induced activation of CaMKII in rat ventricular myocytes
Journal of molecular and cellular cardiology, Vol.48(4), pp.773-780
04/2010
DOI: 10.1016/j.yjmcc.2009.10.020
PMID: 19883656
Abstract
The Ca2+-dependent facilitation (CDF) of L-type Ca2+ channels, a major mechanism for force–frequency relationship of cardiac contraction, is mediated by Ca2+/CaM-dependent kinase II (CaMKII). Recently, CaMKII was shown to be activated by methionine oxidation. We investigated whether oxidation-dependent CaMKII activation is involved in the regulation of L-type Ca2+ currents (ICa,L) by H2O2 and whether Ca2+ is required in this process. Using patch clamp, ICa,L was measured in rat ventricular myocytes. H2O2 induced an increase in ICa,L amplitude and slowed inactivation of ICa,L. This oxidation-dependent facilitation (ODF) of ICa,L was abolished by a CaMKII blocker KN-93, but not by its inactive analog KN-92, indicating that CaMKII is involved in ODF. ODF was not affected by replacement of external Ca2+ with Ba2+ or presence of EGTA in the internal solutions. However, ODF was abolished by adding BAPTA to the internal solution or by depleting sarcoplasmic reticulum (SR) Ca2+ stores using caffeine and thapsigargin. Alkaline phosphatase, β-iminoadenosine 5′-triphosphate (AMP-PNP), an autophosphorylation inhibitor autocamtide-2-related inhibitory peptide (AIP), or a catalytic domain blocker (CaM-KIINtide) did not affect ODF. In conclusion, oxidation-dependent facilitation of L-type Ca2+ channels is mediated by oxidation-dependent CaMKII activation, in which local Ca2+ increases induced by SR Ca2+ release is required.
Details
- Title: Subtitle
- L-type Ca2+ channel facilitation mediated by H2O2-induced activation of CaMKII in rat ventricular myocytes
- Creators
- Young-Hwan Song - Inje University Sanggye Paik HospitalHana Cho - Sungkyunkwan UniversityShin-Young Ryu - New Generation University CollegeJin-Young Yoon - New Generation University CollegeSun-Hyun Park - New Generation University CollegeChung-Il Noh - New Generation University CollegeSuk-Ho Lee - Seoul National UniversityWon-Kyung Ho - New Generation University College
- Resource Type
- Journal article
- Publication Details
- Journal of molecular and cellular cardiology, Vol.48(4), pp.773-780
- Publisher
- Elsevier Ltd
- DOI
- 10.1016/j.yjmcc.2009.10.020
- PMID
- 19883656
- ISSN
- 0022-2828
- eISSN
- 1095-8584
- Language
- English
- Date published
- 04/2010
- Academic Unit
- Cardiovascular Medicine; Internal Medicine
- Record Identifier
- 9984359868502771
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