S-Space College of Medicine/School of Medicine (의과대학/대학원) Pediatrics (소아과학전공) Journal Papers (저널논문_소아과학전공)
L-type Ca(2+) channel facilitation mediated by H(2)O(2)-induced activation of CaMKII in rat ventricular myocytes
- Issue Date
- ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
- JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY; Vol.48(4); 773-780
- Reactive oxygen species ; Ca(2+)/CaM-dependent protein kinase II ; L-type Ca(2+) channels ; L-type Ca(2+) channels ; Sarcoplasmic reticulum Ca(2+) release ; Ca(2+)-dependent facilitation of ; L-type Ca(2+) channels ; Oxidation-dependent facilitation of
- 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.
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