Smooth muscle of telokin-deficient mice exhibits increased sensitivity to Ca2+ and decreased cGMP-induced relaxation

A. S. Khromov, H. Wang, N. Choudhury, M. McDuffie, B. P. Herring, R. Nakamoto, G. K. Owens, A. P. Somlyo, A. V. Somlyo

Research output: Contribution to journalArticle

49 Scopus citations

Abstract

Cyclic nucleotides can relax smooth muscle without a change in [Ca 2+]i, a phenomenon termed Ca2+ desensitization, contributing to vasodilation, gastrointestinal motility, and airway resistance. The physiological importance of telokin, a 17-kDa smooth muscle-specific protein and target for cyclic nucleotide-induced Ca2+ desensitization, was determined in telokin null mice bred to a congenic background. Telokin null ileal smooth muscle homogenates compared to wild type exhibited an ≈30% decrease in myosin light-chain phosphatase (MLCP) activity, which was reflected in a significant leftward shift (up to 2-fold at pCa 6.3) of the Ca2+ force relationship accompanied by an increase in myosin light-chain phosphorylation. No difference in the Ca2+ force relationship occurred in telokin WT and knockout (KO) aortas, presumably reflecting the normally ≈5-fold lower telokin content in aorta vs. ileum smooth muscle. Ca2+ desensitization of contractile force by 8-Br-cGMP was attenuated by 50% in telokin KO intestinal smooth muscle. The rate of force relaxation reflecting MLCP activity, in the presence of 50 μM 8-Br-cGMP, was also significantly slowed in telokin KO vs. WT ileum and was rescued by recombinant telokin. Normal thick filaments in telokin KO smooth muscles indicate that telokin is not required for filament formation or stability. Results indicate that a primary role of telokin is to modulate force through increasing MLCP activity and that this effect is further potentiated through phosphorylation by cGMP in telokin-rich smooth tissues.

Original languageEnglish (US)
Pages (from-to)2440-2445
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume103
Issue number7
DOIs
StatePublished - Feb 14 2006

ASJC Scopus subject areas

  • General

Fingerprint Dive into the research topics of 'Smooth muscle of telokin-deficient mice exhibits increased sensitivity to Ca<sup>2+</sup> and decreased cGMP-induced relaxation'. Together they form a unique fingerprint.

  • Cite this

    Khromov, A. S., Wang, H., Choudhury, N., McDuffie, M., Herring, B. P., Nakamoto, R., Owens, G. K., Somlyo, A. P., & Somlyo, A. V. (2006). Smooth muscle of telokin-deficient mice exhibits increased sensitivity to Ca2+ and decreased cGMP-induced relaxation. Proceedings of the National Academy of Sciences of the United States of America, 103(7), 2440-2445. https://doi.org/10.1073/pnas.0508566103