L-type Ca(2+) channel facilitation mediated by H(2)O(2)-induced activation of CaMKII in rat ventricular myocytes.
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.
Song
Young-Hwan
YH
Department of Pediatrics, Sanggye Paik Hospital, Inje University College of Medicine, Seoul, Korea.
Cho
Hana
H
Ryu
Shin-Young
SY
Yoon
Jin-Young
JY
Park
Sun-Hyun
SH
Noh
Chung-Il
CI
Lee
Suk-Ho
SH
Ho
Won-Kyung
WK
D000266:Adenylyl Imidodiphosphate / Q000737:chemistry; D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D001596:Benzylamines / Q000494:pharmacology; D002110:Caffeine / Q000737:chemistry; D020746:Calcium Channels, L-Type / Q000378:metabolism*; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000378:metabolism*; D020134:Catalytic Domain; D006352:Heart Ventricles / Q000166:cytology*; D006861:Hydrogen Peroxide / Q000737:chemistry*; D008297:Male; D032342:Muscle Cells / Q000166:cytology*; D010100:Oxygen / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D013449:Sulfonamides / Q000494:pharmacology; D019284:Thapsigargin / Q000737:chemistry
D001596:Benzylamines; D020746:Calcium Channels, L-Type; C425780:KN 92; D013449:Sulfonamides; D000266:Adenylyl Imidodiphosphate; D002110:Caffeine; D019284:Thapsigargin; D006861:Hydrogen Peroxide; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D000469:Alkaline Phosphatase; D010100:Oxygen