• We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Logo of biophysjLink to Publisher's site
Biophys J. Aug 2001; 81(2): 1083–1092.
PMCID: PMC1301577

Changes in cardiac contractility related to calcium-mediated changes in phosphorylation of myosin-binding protein C.

Abstract

Ca ions can influence the contraction of cardiac muscle by activating kinases that specifically phosphorylate the myofibrillar proteins myosin-binding protein C (MyBP-C) and the regulatory light chain of myosin (RLC). To investigate the possible role of Ca-regulated phosphorylation of MyBP-C on contraction, isolated quiescent and rhythmically contracting cardiac trabeculae were exposed to different concentrations of extracellular Ca and then chemically skinned to clamp the contractile system. Maximum Ca-activated force (F(max)) was measured in quiescent cells soaking in 1) 2.5 mM Ca for 120 min, 2) 1.25 mM for 120 min, or 3) 1.25 mM for 120 min followed by 10 min in 7.5 mM, and 4) cells rhythmically contracting in 2.5 mM for 20 min. F(max) was, respectively, 21.5, 10.5, 24.7, and 32.6 mN/mm(2). Changes in F(max) were closely associated with changes in the degree of phosphorylation of MyBP-C and occurred at intracellular concentrations of Ca below levels associated with phosphorylation of RLC. Monophosphorylation of MyBP-C by a Ca-regulated kinase is necessary before beta-adrenergic stimulation can produce additional phosphorylation. These results suggest that Ca-dependent phosphorylation of MyBP-C modulates contractility by changing thick filament structure.

Full Text

The Full Text of this article is available as a PDF (371K).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Bassani JW, Bassani RA, Bers DM. Calibration of indo-1 and resting intracellular [Ca]i in intact rabbit cardiac myocytes. Biophys J. 1995 Apr;68(4):1453–1460. [PMC free article] [PubMed]
  • Fabiato A, Fabiato F. Calculator programs for computing the composition of the solutions containing multiple metals and ligands used for experiments in skinned muscle cells. J Physiol (Paris) 1979;75(5):463–505. [PubMed]
  • Gao WD, Backx PH, Azan-Backx M, Marban E. Myofilament Ca2+ sensitivity in intact versus skinned rat ventricular muscle. Circ Res. 1994 Mar;74(3):408–415. [PubMed]
  • Gautel M, Zuffardi O, Freiburg A, Labeit S. Phosphorylation switches specific for the cardiac isoform of myosin binding protein-C: a modulator of cardiac contraction? EMBO J. 1995 May 1;14(9):1952–1960. [PMC free article] [PubMed]
  • Hartzell HC, Glass DB. Phosphorylation of purified cardiac muscle C-protein by purified cAMP-dependent and endogenous Ca2+-calmodulin-dependent protein kinases. J Biol Chem. 1984 Dec 25;259(24):15587–15596. [PubMed]
  • Hasenfuss G, Mulieri LA, Leavitt BJ, Alpert NR. Influence of isoproterenol on contractile protein function, excitation-contraction coupling, and energy turnover of isolated nonfailing human myocardium. J Mol Cell Cardiol. 1994 Nov;26(11):1461–1469. [PubMed]
  • High CW, Stull JT. Phosphorylation of myosin in perfused rabbit and rat hearts. Am J Physiol. 1980 Dec;239(6):H756–H764. [PubMed]
  • Hofmann PA, Hartzell HC, Moss RL. Alterations in Ca2+ sensitive tension due to partial extraction of C-protein from rat skinned cardiac myocytes and rabbit skeletal muscle fibers. J Gen Physiol. 1991 Jun;97(6):1141–1163. [PMC free article] [PubMed]
  • Hofmann PA, Lange JH., 3rd Effects of phosphorylation of troponin I and C protein on isometric tension and velocity of unloaded shortening in skinned single cardiac myocytes from rats. Circ Res. 1994 Apr;74(4):718–726. [PubMed]
  • Hoh JF, Rossmanith GH, Kwan LJ, Hamilton AM. Adrenaline increases the rate of cycling of crossbridges in rat cardiac muscle as measured by pseudo-random binary noise-modulated perturbation analysis. Circ Res. 1988 Mar;62(3):452–461. [PubMed]
  • Holroyde MJ, Small DA, Howe E, Solaro RJ. Isolation of cardiac myofibrils and myosin light chains with in vivo levels of light chain phosphorylation. Biochim Biophys Acta. 1979 Nov 1;587(4):628–637. [PubMed]
  • Janssen PM, de Tombe PP. Protein kinase A does not alter unloaded velocity of sarcomere shortening in skinned rat cardiac trabeculae. Am J Physiol. 1997 Nov;273(5 Pt 2):H2415–H2422. [PubMed]
  • Kardami E, Gratzer WB. Interaction of cardiac myosin and its light chains with calcium ions and regulation of binding by phosphorylation. J Mol Cell Cardiol. 1982 Feb;14(2):73–80. [PubMed]
  • Kentish JC, ter Keurs HE, Ricciardi L, Bucx JJ, Noble MI. Comparison between the sarcomere length-force relations of intact and skinned trabeculae from rat right ventricle. Influence of calcium concentrations on these relations. Circ Res. 1986 Jun;58(6):755–768. [PubMed]
  • Kunst G, Kress KR, Gruen M, Uttenweiler D, Gautel M, Fink RH. Myosin binding protein C, a phosphorylation-dependent force regulator in muscle that controls the attachment of myosin heads by its interaction with myosin S2. Circ Res. 2000 Jan 7;86(1):51–58. [PubMed]
  • Levine RJ, Kensler RW, Yang Z, Stull JT, Sweeney HL. Myosin light chain phosphorylation affects the structure of rabbit skeletal muscle thick filaments. Biophys J. 1996 Aug;71(2):898–907. [PMC free article] [PubMed]
  • Levine R, Weisberg A, Kulikovskaya I, McClellan G, Winegrad S. Multiple structures of thick filaments in resting cardiac muscle and their influence on cross-bridge interactions. Biophys J. 2001 Aug;81(2):1070–1082. [PMC free article] [PubMed]
  • Lin LE, McClellan G, Weisberg A, Winegrad S. A physiological basis for variation in the contractile properties of isolated rat heart. J Physiol. 1991 Sep;441:73–94. [PMC free article] [PubMed]
  • Marban E, Kusuoka H, Yue DT, Weisfeldt ML, Wier WG. Maximal Ca2+-activated force elicited by tetanization of ferret papillary muscle and whole heart: mechanism and characteristics of steady contractile activation in intact myocardium. Circ Res. 1986 Sep;59(3):262–269. [PubMed]
  • Matsubara I, Maughan DW, Saeki Y, Yagi N. Cross-bridge movement in rat cardiac muscle as a function of calcium concentration. J Physiol. 1989 Oct;417:555–565. [PMC free article] [PubMed]
  • McClellan G, Weisberg A, Winegrad S. Energy transport from mitochondria to myofibril by a creatine phosphate shuttle in cardiac cells. Am J Physiol. 1983 Nov;245(5 Pt 1):C423–C427. [PubMed]
  • McClellan G, Weisberg A, Winegrad S. cAMP can raise or lower cardiac actomyosin ATPase activity depending on alpha-adrenergic activity. Am J Physiol. 1994 Aug;267(2 Pt 2):H431–H442. [PubMed]
  • McClellan G, Weisberg A, Winegrad S. Effect of endothelin-1 on actomyosin ATPase activity. Implications for the efficiency of contraction. Circ Res. 1996 Jun;78(6):1044–1050. [PubMed]
  • Offer G, Moos C, Starr R. A new protein of the thick filaments of vertebrate skeletal myofibrils. Extractions, purification and characterization. J Mol Biol. 1973 Mar 15;74(4):653–676. [PubMed]
  • Saeki Y, Kawai M, Zhao Y. Comparison of crossbridge dynamics between intact and skinned myocardium from ferret right ventricles. Circ Res. 1991 Mar;68(3):772–781. [PubMed]
  • Schlender KK, Bean LJ. Phosphorylation of chicken cardiac C-protein by calcium/calmodulin-dependent protein kinase II. J Biol Chem. 1991 Feb 15;266(5):2811–2817. [PubMed]
  • Silver PJ, Buja LM, Stull JT. Frequency-dependent myosin light chain phosphorylation in isolated myocardium. J Mol Cell Cardiol. 1986 Jan;18(1):31–37. [PubMed]
  • Solaro RJ, Pang DC, Briggs FN. The purification of cardiac myofibrils with Triton X-100. Biochim Biophys Acta. 1971 Aug 6;245(1):259–262. [PubMed]
  • Solaro RJ, Van Eyk J. Altered interactions among thin filament proteins modulate cardiac function. J Mol Cell Cardiol. 1996 Feb;28(2):217–230. [PubMed]
  • Strang KT, Sweitzer NK, Greaser ML, Moss RL. Beta-adrenergic receptor stimulation increases unloaded shortening velocity of skinned single ventricular myocytes from rats. Circ Res. 1994 Mar;74(3):542–549. [PubMed]
  • Stull JT, Manning DR, High CW, Blumenthal DK. Phosphorylation of contractile proteins in heart and skeletal muscle. Fed Proc. 1980 Apr;39(5):1552–1557. [PubMed]
  • Sweeney HL, Stull JT. Phosphorylation of myosin in permeabilized mammalian cardiac and skeletal muscle cells. Am J Physiol. 1986 Apr;250(4 Pt 1):C657–C660. [PubMed]
  • Weisberg A, Winegrad S. Relation between crossbridge structure and actomyosin ATPase activity in rat heart. Circ Res. 1998 Jul 13;83(1):60–72. [PubMed]

Articles from Biophysical Journal are provided here courtesy of The Biophysical Society

Formats:

Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...

Links

  • Compound
    Compound
    PubChem Compound links
  • MedGen
    MedGen
    Related information in MedGen
  • PubMed
    PubMed
    PubMed citations for these articles
  • Substance
    Substance
    PubChem Substance links

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...