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L-type Ca(2+) Channel Facilitation Mediated by H(2)O(2)-induced Activation of CaMKII in Rat Ventricular Myocytes

L-type Ca(2+) Channel Facilitation Mediated by H(2)O(2)-induced Activation of CaMKII in Rat Ventricular Myocytes

Young-Hwan Song, Hana Cho, Shin-Young Ryu, Jin-Young Yoon, Sun-Hyun Park, Chung-Il Noh, Suk-Ho Lee, Won-Kyung Ho

J Mol Cell Cardiol. 2010 Apr;48(4):773-80.

PMID: 19883656

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 BAPTA 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 (AIP), 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.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
IAR42415241	Calmodulin Kinase IINtide			Price

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