title: The troponin I: inhibitory peptide uncouples force generation and the cooperativity of contractile activation in mammalian skeletal muscle.
abstract: Hodges and his colleagues identified a 12 amino acid fragment of troponin I (TnI-ip) that inhibits Ca(2+)-activated force and reduces the effectiveness Ca(2+) as an activator. To understand the role of troponin C (TnC) in the extended cooperative interactions of thin filament activation, we compared the effect of TnI-ip with that of partial troponin TnC extraction. Both methods reduce maximal Ca(2+)-activated force and increase [Ca(2+)] required for activation. In contrast to TnC extraction, TnI-ip does not reduce the extended cooperative interactions between adjacent thin filament regulatory units as assessed by the slope of the pCa/force relationship. Additional evidence that TnI-ip does not interfere with extended cooperativity comes from studies that activate muscle by rigor crossbridges (RXBs). TnI-ip increases both the cooperativity of activation and the concentration of RXBs needed for maximal force. This shows that TnI-ip binding to TnC increases the stability of the relaxed state of the thin filament. TnI-ip, therefore, uncouples force generation from extended cooperativity in both Ca(2+) and RXB activated muscle contraction. Because maximum force can be reduced with no change-or even an increase-in cooperativity, force-generating crossbridges do not appear to be the primary activators of cooperativity between thin filament regulatory units of skeletal muscle.
authors: Division of Physiology, Department of Cell Biology, Duke University Medical School, Box 3011, Durham, NC, 27710, USA. f.schachat@cellbio.duke.edu
authors: Fred
authors: F
authors: Schachat
authors: Philip W
authors: PW
authors: Brandt
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D053580:Muscle Strength / Q000187:drug effects*; D018482:Muscle, Skeletal / Q000378:metabolism*; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D011817:Rabbits; D019209:Troponin C / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D019210:Troponin I / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D010446:Peptide Fragments; D019209:Troponin C; D019210:Troponin I; C061291:troponin I (104-115); D002118:Calcium