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This Article Full Text Full Text (PDF) All Versions of this Article: 564/2/603    most recent jphysiol.2005.083238v1 Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Sarin, V. Articles by Muthuchamy, M. Search for Related Content PubMed PubMed Citation Articles by Sarin, V. Articles by Muthuchamy, M.

¹ Department of Medical Physiology, Cardiovascular Research Institute, 336 Reynolds Medical Building, Texas A & M University System Health Science Center, College of Medicine, College Station, TX 77843-1114, USA

Integrins are considered to be an important mechanosensor in cardiac myocytes. To test whether integrins can influence cardiac contractile function, the force–frequency relationships of mouse papillary muscle bundles were measured in the presence or absence of a synthetic integrin-binding peptide, GRGDNP (gly–arg–gly–asp–asn–pro). Results demonstrate that in the presence of an arginine–glycine–aspartic acid (RGD)-containing synthetic peptide, contractile force was depressed significantly by, 28% at 4 Hz, 37.7% at 5 Hz and 20% at 10 Hz (n = 6, P < 0.01). Treatment of myofibres with either protease-generated fragments of denatured collagen (Type I) or denatured collagen that contain the RGD motif, also reduced force production significantly. An integrin-activating antibody for ß₁ integrin inhibited the force similar to synthetic RGD peptide. Function-blocking integrin antibodies for ₅ and ß₁ integrins reversed the effect of the RGD-containing peptide, and ₅ integrin also reversed the effect of proteolytic fragments of denatured collagen on contractile force, whereas experiments with function-blocking antibody for ß₃ integrin did not reverse the effect of RGD peptide. Force–[Ca²⁺]_i measurements showed that the depressed rate of force generation observed in the presence of the RGD-containing peptide was associated with reduced [Ca²⁺]_i. Data analyses further demonstrated that force per unit of Ca²⁺ was reduced, suggesting that the myofilament activation process was altered. In addition, inhibition of PKC enzyme using the selective, cell-permeable inhibitor Ro-32-0432, reversed the activity of RGD peptide on papillary muscle bundles. In conclusion, these data indicate that RGD peptide, acting via ₅ß₁ integrin, depresses the force production from papillary muscle bundles, partly associated with changes in [Ca²⁺]_i and the myofilament activation processes, that is modulated by PKC.

(Received 13 January 2005; accepted after revision 11 February 2005; first published online 17 February 2005)
Corresponding authors G. A. Meininger and M. Muthuchamy: Department of Medical Physiology, Cardiovascular Research Institute, 336 Reynolds Medical Building, Texas A & M University System Health Science Center, College of Medicine, College Station, TX 77843-1114, USA. Email: marim{at}tamu.edu and gam{at}tamu.edu

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