Orientational Changes of Troponin C Associated with Thin Filament Activation

Biochemistry ◽  
1994 ◽  
Vol 33 (47) ◽  
pp. 14324-14332 ◽  
Author(s):  
Hui-Chun Li ◽  
Piotr G. Fajer
Keyword(s):  
Thin Filament ◽  
Troponin C ◽  
Filament Activation

scholarly journals Kinetics of a Ca(2+)-sensitive cross-bridge state transition in skeletal muscle fibers. Effects due to variations in thin filament activation by extraction of troponin C.

1991 ◽  
Vol 98 (2) ◽  
pp. 233-248 ◽  
Author(s):  
J M Metzger ◽  
R L Moss
Keyword(s):  
Steady State ◽  
Direct Effect ◽  
Thin Filament ◽  
Near Neighbor ◽  
Troponin C ◽  
Isometric Tension ◽  
Cross Bridge ◽  
Filament Activation ◽  
Kinetics Of ◽  
Partial Extraction

The rate constant of tension redevelopment (ktr; 1986. Proc. Natl. Acad. Sci. USA. 83:3542-3546) was determined at various levels of thin filament activation in skinned single fibers from mammalian fast twitch muscles. Activation was altered by (a) varying the concentration of free Ca2+ in the activating solution, or (b) extracting various amounts of troponin C (TnC) from whole troponin complexes while keeping the concentration of Ca2+ constant. TnC was extracted by bathing the fiber in a solution containing 5 mM EDTA, 10 mM HEPES, and 0.5 mM trifluoperazine dihydrochloride. Partial extraction of TnC resulted in a decrease in the Ca2+ sensitivity of isometric tension, presumably due to disruption of near-neighbor molecular cooperativity between functional groups (i.e., seven actin monomers plus associated troponin and tropomyosin) within the thin filament. Altering the level of thin filament activation by partial extraction of TnC while keeping Ca2+ concentration constant tested whether the Ca2+ sensitivity of ktr results from a direct effect of Ca2+ on cross-bridge state transitions or, alternatively, an indirect effect of Ca2+ on these transitions due to varying extents of thin filament activation. Results showed that the ktr-pCa relation was unaffected by partial extraction of TnC, while steady-state isometric tension exhibited the expected reduction in Ca2+ sensitivity. This finding provides evidence for a direct effect of Ca2+ on an apparent rate constant that limits the formation of force-bearing cross-bridge states in muscle fibers. Further, the kinetics of this transition are unaffected by disruption of near-neighbor thin filament cooperativity subsequent to extraction of TnC. Finally, the results support the idea that the steepness of the steady-state isometric tension-calcium relationship is at least in part due to mechanisms involving molecular cooperativity among thin filament regulatory proteins.

scholarly journals Influence of enhanced troponin C Ca2+-binding affinity on cooperative thin filament activation in rabbit skeletal muscle

2007 ◽  
Vol 583 (1) ◽  
pp. 337-350 ◽  
Author(s):  
Kareen L. Kreutziger ◽  
Todd E. Gillis ◽  
Jonathan P. Davis ◽  
Svetlana B. Tikunova ◽  
Michael Regnier
Keyword(s):  
Skeletal Muscle ◽  
Binding Affinity ◽  
Thin Filament ◽  
Troponin C ◽  
Rabbit Skeletal Muscle ◽  
Filament Activation

scholarly journals Kinetics of Cardiac Thin-Filament Activation Probed by Fluorescence Polarization of Rhodamine-Labeled Troponin C in Skinned Guinea Pig Trabeculae

2006 ◽  
Vol 90 (2) ◽  
pp. 531-543 ◽  
Author(s):  
Marcus G. Bell ◽  
Edward B. Lankford ◽  
Gregory E. Gonye ◽  
Graham C.R. Ellis-Davies ◽  
Donald A. Martyn ◽  
...  
Keyword(s):  
Guinea Pig ◽  
Fluorescence Polarization ◽  
Thin Filament ◽  
Troponin C ◽  
Filament Activation ◽  
Kinetics Of

scholarly journals Increased thin filament activation enhances alternans in human chronic atrial fibrillation

2018 ◽  
Vol 315 (5) ◽  
pp. H1453-H1462 ◽  
Author(s):  
Melanie A. Zile ◽  
Natalia A. Trayanova
Keyword(s):  
Atrial Fibrillation ◽  
Action Potential ◽  
Single Cell ◽  
Action Potential Duration ◽  
Thin Filament ◽  
Chronic Atrial Fibrillation ◽  
Troponin C ◽  
Protein Kinetics ◽  
Intracellular Ca ◽  
Filament Activation

Action potential duration (APD) alternans (APD-ALT), defined as beat-to-beat oscillations in APD, has been proposed as an important clinical marker for chronic atrial fibrillation (cAF) risk when it occurs at pacing rates of 120–200 beats/min. Although the ionic mechanisms for occurrence of APD-ALT in human cAF at these clinically relevant rates have been investigated, little is known about the effects of myofilament protein kinetics on APD-ALT. Therefore, we used computer simulations of single cell function to explore whether remodeling in myofilament protein kinetics in human cAF alters the occurrence of APD-ALT and to uncover how these mechanisms are affected by sarcomere length and the degree of cAF-induced myofilament remodeling. Mechanistically based, bidirectionally coupled electromechanical models of human right and left atrial myocytes were constructed, incorporating both ionic and myofilament remodeling associated with cAF. By comparing results from our electromechanical model with those from the uncoupled ionic model, we found that intracellular Ca2+ concentration buffering of troponin C has a dampening effect on the magnitude of APD-ALT (APD-ANM) at slower rates (150 beats/min) due to the cooperativity between strongly bound cross-bridges and Ca2+-troponin C binding affinity. We also discovered that cAF-induced enhanced thin filament activation enhanced APD-ANM at these clinically relevant heart rates (150 beats/min). In addition, longer sarcomere lengths increased APD-ANM, suggesting that atrial stretch is an important modulator of APD-ALT. Together, these findings demonstrate that myofilament kinetics mechanisms play an important role in altering APD-ALT in human cAF. NEW & NOTEWORTHY Using a single cell simulation approach, we explored how myofilament protein kinetics alter the formation of alternans in action potential duration (APD) in human myocytes with chronic atrial fibrillation remodeling. We discovered that enhanced thin filament activation and longer sarcomere lengths increased the magnitude of APD alternans at clinically important pacing rates of 120–200 beats/min. Furthermore, we found that altered intracellular Ca2+ concentration buffering of troponin C has a dampening effect on the magnitude of APD alternans.

scholarly journals Contributions of Ca 2+ -Independent Thin Filament Activation to Cardiac Muscle Function

2015 ◽  
Vol 109 (10) ◽  
pp. 2101-2112 ◽  
Author(s):  
Yasser Aboelkassem ◽  
Jordan A. Bonilla ◽  
Kimberly J. McCabe ◽  
Stuart G. Campbell
Keyword(s):  
Cardiac Muscle ◽  
Muscle Function ◽  
Thin Filament ◽  
Filament Activation

scholarly journals Cardiac Thin Filament Activation Modulation by Stretch

2013 ◽  
Vol 104 (2) ◽  
pp. 453a
Author(s):  
Younss Ait Mou ◽  
Pieter P. de Tombe
Keyword(s):  
Thin Filament ◽  
Filament Activation
Sign in / Sign up

Export Citation Format

Share Document