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Ca 2+ ‐calmodulin‐dependent protein kinase II‐dependent activation of contractility in ferret aorta
Author(s) -
Kim Inkyeom,
Je HyunDong,
Gallant Cynthia,
Zhan Qian,
Riper Dee Van,
Badwey John A.,
Singer Harold A.,
Morgan Kathleen G.
Publication year - 2000
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1111/j.1469-7793.2000.00367.x
Subject(s) - chemistry , contractility , calmodulin , contraction (grammar) , protein kinase a , myosin light chain kinase , kinase , endocrinology , mapk/erk pathway , medicine , phosphorylation , protein kinase c , muscle contraction , phenylephrine , calcium , biochemistry , biology , organic chemistry , blood pressure
1 The present study was undertaken to determine whether Ca 2+ ‐calmodulin‐dependent protein kinase II (CaMKII) participates in the regulation of vascular smooth muscle contraction, and if so, to investigate the nature of the downstream effectors. 2 The contractility of isolated ferret aorta was measured while inhibiting CaMKII either with antisense oligodeoxynucleotides against CaMKII or with the CaMKII inhibitor KN93. 3 Treatment with antisense oligodeoxynucleotides against CaMKII resulted in, on average, a decrease in protein levels of CaMKII to 56 % of control levels and significantly decreased the magnitude of the contraction in response to 51 m m potassium physiological saline solution (KCl). Contraction in response to the phorbol ester DPBA was not significantly affected. 4 The CaMKII blocker KN93 also resulted in a significant decrease in the force induced by 51 m m KCl but caused no significant change in the contraction in response to DPBA or the α‐adrenoceptor agonist phenylephrine. 5 During contraction with 51 m m KCl, both CaMKII and mitogen‐activated protein kinase (MAPK) activity increased, as determined by phospho‐specific antibodies. The MAPK phosphorylation level was inhibited by KN93, PD098059 (a MAPK kinase (MEK) inhibitor) and calcium depletion. 6 Myosin light chain (LC20) phosphorylation also increased during contraction with KCl and the increase was significantly blocked by PD098059 as well as by both KN93 and antisense oligodeoxynucleotides to CaMKII. 7 The data indicate that CaMKII plays a significant role in the regulation of smooth muscle contraction and suggest that CaMKII activates a pathway by which MAPK activation leads to phosphorylation of LC20 via activation of myosin light chain kinase.