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L-type Ca(2+) channel facilitation mediated by H(2)O(2)-induced activation of CaMKII in rat ventricular myocytes

Cited 44 time in Web of Science Cited 47 time in Scopus
Issue Date
2010-04
Publisher
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
Citation
JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY; Vol.48(4); 773-780
Keywords
Reactive oxygen speciesCa(2+)/CaM-dependent protein kinase IIL-type Ca(2+) channelsL-type Ca(2+) channelsSarcoplasmic reticulum Ca(2+) releaseCa(2+)-dependent facilitation ofL-type Ca(2+) channelsOxidation-dependent facilitation of
Abstract
The Ca(2+)-dependent facilitation (CDF) of L-type Ca(2+) channels, a major mechanism for force-frequency relationship of cardiac contraction, is mediated by Ca(2+)/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 Ca(2+) currents (I(Ca.L)) by H(2)O(2) and whether Ca(2+) is required in this process. Using patch clamp, I(Ca,L) was measured in rat ventricular myocytes. H(2)O(2) induced an increase in I(Ca,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 Ca(2+) with Ba(2+) 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) Ca(2+) 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 Ca(2+) channels is mediated by oxidation-dependent CaMKII activation, in which local Ca(2+) increases induced by SR Ca(2+) release is required.
ISSN
0022-2828
Language
English
URI
https://hdl.handle.net/10371/77709
DOI
https://doi.org/10.1016/j.yjmcc.2009.10.020
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College of Medicine/School of Medicine (의과대학/대학원)Pediatrics (소아과학전공)Journal Papers (저널논문_소아과학전공)
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