Journal
JOURNAL OF MUSCLE RESEARCH AND CELL MOTILITY
Volume 31, Issue 3, Pages 227-239Publisher
SPRINGER
DOI: 10.1007/s10974-010-9228-3
Keywords
Tropomyosin isoforms; Thin filament regulation; Calcium sensitivity; Muscle contraction; Transgenic mice
Categories
Funding
- National Institutes of Health [HL71952, HL081680, HL22231, HL 62426, K01 HL67709]
Ask authors/readers for more resources
Tropomyosin (TM) plays a central role in calcium mediated striated muscle contraction. There are three muscle TM isoforms: alpha-TM, beta-TM, and gamma-TM. alpha-TM is the predominant cardiac and skeletal muscle isoform. beta-TM is expressed in skeletal and embryonic cardiac muscle. gamma-TM is expressed in slow-twitch musculature, but is not found in the heart. Our previous work established that muscle TM isoforms confer different physiological properties to the cardiac sarcomere. To determine whether one of these isoforms is dominant in dictating its functional properties, we generated single and double transgenic mice expressing beta-TM and/or gamma-TM in the heart, in addition to the endogenously expressed alpha-TM. Results show significant TM protein expression in the beta gamma-DTG hearts: alpha-TM: 36%, beta-TM: 32%, and gamma-TM: 32%. These beta gamma-DTG mice do not develop pathological abnormalities; however, they exhibit a hyper contractile phenotype with decreased myofilament calcium sensitivity, similar to gamma-TM transgenic hearts. Biophysical studies indicate that gamma-TM is more rigid than either alpha-TM or beta-TM. This is the first report showing that with approximately equivalent levels of expression within the same tissue, there is a functional dominance of gamma-TM over alpha-TM or beta-TM in regulating physiological performance of the striated muscle sarcomere. In addition to the effect expression of gamma-TM has on Ca2+ activation of the cardiac myofilaments, our data demonstrates an effect on cooperative activation of the thin filament by strongly bound rigor cross-bridges. This is significant in relation to current ideas on the control mechanism of the steep relation between Ca2+ and tension.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available