Modulation of smooth muscle tonus in the lower urinary tract: interplay of myosin light-chain kinase (MLCK) and MLC phosphatase (MLCP).
Modulation of smooth muscle tonus in the lower urinary tract: interplay of myosin light-chain kinase (MLCK) and MLC phosphatase (MLCP).
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DOI：
10.1111/j.1464-410x.2010.09819.x
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发表时间：
2011-07
影响因子：
4.5
通讯作者：
Lin CS
中科院分区：
文献类型：
--
作者：
Lin G;Fandel TM;Shindel AW;Wang G;Banie L;Ning H;Lue TF;Lin CS
Smooth muscle tonus in the bladder and urethra plays a critical role in the normal function of the lower urinary tract. The phosphorylation status of the myosin light chain (MLC) is a key regulator of smooth muscle tonus. MLC phosphorylation is modulated by myosin light chain kinase (MLCK) and myosin light chain phosphatase (MLCP). We investigated expression and activity of MLCK and MLCP in the rat bladder and urethra. Bladder and urethral smooth muscles were obtained from 2-month-old female Sprague Dawley rats. Real-time PCR and Western blotting were used to assess expression of MLCK and myosin phosphatase-targeting subunit of protein phosphatase type 1 (MYPT1), an inhibitor of MLCP. A two-step enzymatic activity assay using phosphorylated and dephosphorylated smooth muscle myosin was used to assess MLCK and MLCP activity. MLCK mRNA expression was higher in the bladder than the urethra but this difference was not statistically significant (0.26 ± 0.17 vs. 0.14 ± 0.12, p = 0.09). MYPT1 mRNA expression was significantly higher in the bladder than the urethra (2.31 ± 1.04 vs. 0.56 ± 0.36, p = 0.001). Expression of both MLCK and MYPT1 protein was significantly higher in the bladder compared to the urethra (1.63 ± 0.25 vs. 0.91 ± 0.29 and 0.97 ± 0.10 vs. 0.37 ± 0.29, respectively, p <0.001 for both). Functional enzymatic assay identified significantly greater MLCK activity in the bladder compared to the urethra. MLCP activity was lower in the bladder compared to the urethra but the difference was statistically significant only at 1 minute after initiation of assay. In healthy young female rats, MLCK activity is higher and MLCP activity lower in the bladder relative to the urethra. These differences likely play a role in modulating the functional differences between bladder and urethral smooth muscle tone.
