These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: Identification of two new regions in the N-terminus of cardiac troponin T that have divergent effects on cardiac contractile function.
    Author: Mamidi R, Mallampalli SL, Wieczorek DF, Chandra M.
    Journal: J Physiol; 2013 Mar 01; 591(5):1217-34. PubMed ID: 23207592.
    Abstract:
    Abstract  Cardiac troponin T (cTnT) has a highly acidic extended N-terminus, the physiological role of which remains poorly understood. To decipher the physiological role of this unique region, we deleted specific regions within the N-terminus of mouse cTnT (McTnT) to create McTnT1-44 and McTnT45-74 proteins. Contractile function and dynamic force-length measurements were made after reconstituting the McTnT deletion proteins into detergent-skinned cardiac papillary fibres harvested from non-transgenic mice that expressed α-tropomyosin (Tm). To further understand how the functional effects of the N-terminus of cTnT are modulated by Tm isoforms, McTnT deletion proteins were reconstituted into detergent-skinned cardiac papillary fibres harvested from transgenic mice that expressed both α- and β-Tm. McTnT1-44, but not McTnT45-74, attenuated maximal activation of the thin filament. Myofilament Ca(2+) sensitivity, as measured by pCa50 (-log of [Ca(2+)]free required for half-maximal activation), decreased in McTnT1-44 (α-Tm) fibres. The desensitizing effect of McTnT1-44 on pCa50 was ablated in β-Tm fibres. McTnT45-74 enhanced pCa50 in both α- and β-Tm fibres, with β-Tm having a bigger effect. The Hill coefficient of tension development was significantly attenuated by McTnT45-74, suggesting an effect on thin-filament cooperativity. The rate of cross-bridge (XB) detachment and the strained XB-mediated impact on other XBs were augmented by McTnT1-44 in β-Tm fibres. The magnitude of the length-mediated recruitment of XBs was attenuated by McTnT1-44 in β-Tm fibres. Our data demonstrate that the 1-44 region of McTnT is essential for maximal activation, whereas the cardiac-specific 45-74 region of McTnT is essential for augmenting cooperativity. Moreover, our data show that α- and β-Tm isoforms have divergent effects on McTnT deletion mutant's ability to modulate cardiac thin-filament activation and Ca(2+) sensitivity. Our results not only provide the first explicit evidence for the existence of two distinct functional regions within the N-terminus of cTnT, but also offer mechanistic insights into the divergent physiological roles of these regions in mediating cardiac contractile activation.
    [Abstract] [Full Text] [Related] [New Search]