Staurosporine inhibits frequency-dependent myofilament desensitization in intact rabbit cardiac trabeculae.
Staurosporine inhibits frequency-dependent myofilament desensitization in intact rabbit cardiac trabeculae.
复制标题
星形孢菌素抑制完整兔心脏小梁中频率依赖性肌丝脱敏。
DOI：
10.1155/2012/290971
复制
发表时间：
2012
影响因子：
3
通讯作者：
Janssen,PaulML
中科院分区：
文献类型：
--
作者：
Varian,KennethD;Biesiadecki,BrandonJ;Ziolo,MarkT;Davis,JonathanP;Janssen,PaulML
Myofilament calcium sensitivity decreases with frequency in intact healthy rabbit trabeculae and associates with Troponin I and Myosin light chain‐2 phosphorylation. We here tested whether serine‐threonine kinase activity is primarily responsible for this frequency‐dependent modulations of myofilament calcium sensitivity. Right ventricular trabeculae were isolated from New Zealand White rabbit hearts and iontophoretically loaded with bis‐fura‐2. Twitch force‐calcium relationships and steady state force‐calcium relationships were measured at frequencies of 1 and 4 Hz at 37 °C. Staurosporine (100 nM), a nonspecific serine‐threonine kinase inhibitor, or vehicle (DMSO) was included in the superfusion solution before and during the contractures. Staurosporine had no frequency‐dependent effect on force development, kinetics, calcium transient amplitude, or rate of calcium transient decline. The shift in the pCa50of the force‐calcium relationship was significant from 6.05 ± 0.04 at 1 Hz versus 5.88 ± 0.06 at 4 Hz under control conditions (vehicle,P< 0.001) but not in presence of staurosporine (5.89 ± 0.08 at 1 Hz versus 5.94 ± 0.07 at 4 Hz,P= NS). Phosphoprotein analysis (Pro‐Q Diamond stain) confirmed that staurosporine significantly blunted the frequency‐dependent phosphorylation at Troponin I and Myosin light chain‐2. We conclude that frequency‐dependent modulation of calcium sensitivity is mediated through a kinase‐specific effect involving phosphorylation of myofilament proteins.
