Activation of nitric oxide synthase (NOS3) by mechanical activity alters contractile activity in a Ca2+-independent manner in cardiac myocytes:: Role of troponin I phosphorylation

被引:26
作者
Kaye, DM
Wiviott, SD
Kelly, RA
机构
[1] Brigham & Womens Hosp, Dept Med, Div Cardiovasc, Boston, MA 02115 USA
[2] Harvard Univ, Sch Med, Boston, MA 02115 USA
关键词
fura-2; troponin I; phosphorylation; methylene blue; L-nitroarginine;
D O I
10.1006/bbrc.1999.0346
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Cardiac myocytes express the calcium-responsive nitric oxide synthase (eNOS or NOS3). Activation of NOS3 by increased intracellular Ca2+ concentration, [Ca2+](i), has been demonstrated to decrease myocyte contractile responsiveness, although this appears to occur in a Ca2+-independent manner. Therefore, the aim of this study was to examine the possibility that contractile activity could be modulated by an NO-mediated alteration in the phosphorylation status of troponin I, which is known to alter myofilament sensitivity to Ca2+. During pacing at 3 Hz, P-32-labeled myocytes exhibited a 59 +/- 9% increase in TnI phosphorylation compared to quiescent cells (p < 0.05), an effect that was significantly attenuated by either methylene blue or L-nitroarginine (L-NA), While exposure to methylene blue significantly increased the contractile amplitude of paced myocytes, this was not accompanied by an alteration in intracellular Ca2+. These data indicate that the NO-mediated effects on myocyte contraction may be elicited through an alteration in myofilament Ca2+ sensitivity that results from an alteration in the phosphorylation status of troponin I. (C) 1999 Academic Press.
引用
收藏
页码:398 / 403
页数:6
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