期刊
JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY
卷 48, 期 4, 页码 773-780出版社
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.yjmcc.2009.10.020
关键词
Reactive oxygen species; Ca2+/CaM-dependent protein kinase II; L-type Ca2+ channels; Oxidation-dependent facilitation of; L-type Ca2+ channels; Ca2+-dependent facilitation of; L-type Ca2+ channels; Sarcoplasmic reticulum Ca2+ release
资金
- Korean Ministry of Education, Science and Technology [R0A-2004-000-10295-0]
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 (I-Ca.L) by H2O2 and whether Ca2+ is required in this process. Using patch clamp, I-Ca,I-L was measured in rat ventricular myocytes. H2O2 induced an increase in I-Ca,I-L amplitude and slowed inactivation of I-Ca.L. This oxidation-dependent facilitation (ODF) of I-ca, 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 BAFTA to the internal solution or by depleting sarcoplasmic reticulum (SR) Ca2+ stores using caffeine and thapsigargin. Alkaline phosphatase, beta-iminoadenosine 5'-triphosphate (AMP-PNP), an autophosphorylation inhibitor autocamtide-2-related inhibitory peptide (Alp), 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. (c) 2009 Elsevier Ltd. All rights reserved.
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