Abstract
Ventricular myocytes are continuously exposed to fluid shear in vivo by relative movement of laminar sheets and adjacent cells. Preliminary observations have shown that neonatal myocytes respond to fluid shear by increasing their beating rate, which could have an arrhythmogenic effect under elevated shear conditions. The objective of this study is to investigate the characteristics of the fluid shear response in cultured myocytes and to study selected potential mechanisms. Cultured neonatal rat ventricular myocytes that were spontaneously beating were subjected to low shear rates (5–50/s) in a fluid flow chamber using standard culture medium. The beating rate was measured from digital microscopic recordings. The myocytes reacted to low shear rates by a graded and reversible increase in their spontaneous beating rate of up to 500%. The response to shear was substantially attenuated in the presence of the β-adrenergic agonist isoproterenol (by 86±8%), as well as after incubation with integrin-blocking RGD peptides (by 92±8%). The results suggest that the β-adrenergic signaling pathway and integrin activation, which are known to interact, may play an important role in the response mechanism.
Similar content being viewed by others
References
Dou, J., Tseng, W. Y., Reese, T. G., and Wedeen, V. J. (2003) Combined diffusion and strain MRI reveals structure and function of human myocardial laminar sheets in vivo. Magn. Reson. Med. 50, 107–113.
Dewey, C. F., Jr., Bussolari, S. R., Gimbrone, M. A., Jr., and Davies, P. F. (1981) The dynamic response of vascular endothelial cells to fluid shear stress. J. Biomech. Eng. 103, 177–185.
Sterpetti, A. V., Cucina, A., D'Angelo, L. S., Cardillo, B., and Cavallaro, A. (1992) Response of arterial smooth muscle cells to laminar flow. J. Cardiovasc. Surg. (Torino) 33, 619–624.
Moazzam, F., DeLano, F. A., Zweifach, B. W., and Schmid-Schonbein, G. W. (1997) The leukocyte response to fluid stress. Proc. Natl. Acad. Sci. USA 94, 5338–5343.
Coughlin, M. F., and Schmid-Schonbein, G. W. (2004) Pseudopod projection and cell spreading of passive leukocytes in response to fluid shear stress. Biophys. J. 87, 2035–2042.
Klein-Nulend, J., van der Plas, A., Semeins, C. M., et al. (1995) Sensitivity of osteocytes to biomechanical stress in vitro. FASEB J. 9, 441–445.
Belval, T., Hellums, J. D., and Solis, R. T. (1984) The kinetics of platelet aggregation induced by fluid-shearing stress. Microvasc. Res. 28, 279–288.
Nauli, S. M., Alenghat, F. J., Luo, Y., et al. (2003) Polycystins 1 and 2 mediate mechanosensation in the primary cilium of kidney cells. Nat. Genet. 33, 129–137.
Davies, P. F. (1995) Flow-mediated endothelial mechanotransduction. Physiol. Rev. 75, 519–560.
Kong, C. R., Bursac, N., and Tung, L. (2005) Mechanoelectrical excitation by fluid jets in monolayers of cultured cardiac myocytes. J. Appl. Physiol. 98, 2328–2336.
Gopalan, S. M., Flaim, C., Bhatia, S. N., et al. (2003). Anisotropic stretch-induced hypertrophy in neonatal ventricular myocytes micropatterned on deformable elastomers. Biotechnol. Bioeng. 81, 578–587.
Torsoni, A. S., Constancio, S. S., Nadruz, W., Jr., Hanks, S. K., and Franchini, K. G. (2003) Focal adhesion kinase is activated and mediates the early hypertrophic response to stretch in cardiac myocytes. Circ. Res. 93, 140–147.
Shyu, K. G., Chen, C. C., Wang, B. W., and Kuan, P. (2001) Angiotensin II receptor antagonist blocks the expression of connexin43 induced by cyclical mechanical stretch in cultured neonatal rat cardiac myocytes. J. Mol. Cell. Cardiol. 33, 691–698.
Tanaka, N., Mao, L., DeLano, F. A., et al. (1997) Left ventricular volumes and function in the embryonic mouse heart. Am. J. Physiol. 273, H1368-H1376.
Paul, S. (2003) Ventricular remodeling. Crit. Care Nurs. Clin. N. Am. 15, 407–411.
Masuda, H., and Sperelakis, N. (1993) Inwardly rectifying potassium current in rat fetal and neonatal ventricular cardiomyocytes. Am. J. Physiol. 265, H1107-H1111.
Gomez, J. P., Potreau, D., and Raymond, G. (1994) Intracellular calcium transients from newborn rat cardiomyocytes in primary culture. Cell Calcium 15, 265–276.
Cerbai, E., Pino, R., Sartiani, L., and Mugelli, A. (1999) Influence of postnatal-development of I(f) occurrence and properties in neonatal rat ventricular myocytes. Cardiovasc. Res. 42, 416–423.
Kimura, H., Takemura, H., Imoto, K., Furukawa, K., Ohshika, H., and Mochizuki, Y. (1998) Relation between spontaneous contraction and sarcoplasmic reticulum function in cultured neonatal rat cardiac myocytes. Cell Signal 10, 349–354.
Lakatta, E. G. (2004) Beyond Bowditch: the convergence of cardiac chronotropy and inotropy. Cell Calcium 35, 629–642.
Silva, J., and Rudy, Y. (2003) Mechanism of pacemaking in I(K1)-downregulated myocytes. Circ. Res. 92, 261–263.
Xiang, Y., Rybin, V. O., Steinberg, S. F., and Kobilka, B. (2002) Caveolar localization dictates physiologic signaling of beta 2-adrenoceptors in neonatal cardiac myocytes. J. Biol. Chem. 277, 34,280–34,286.
Abi-Gerges, N., Fischmeister, R., and Mery, P. F. (2001) G protein-mediated inhibitory effect of a nitric oxide donor on the L-type Ca2+ current in rat ventricular myocytes. J. Physiol. 531, 117–130.
Balligand, J. L., Kelly, R. A., Marsden, P. A., Smith, T. W., and Michel, T. (1993) Control of cardiac muscle cell function by an endogenous nitric oxide signaling system. Proc. Natl. Acad. Sci. USA 90, 347–351.
Devic, E., Xiang, Y., Gould, D., and Kobilka, B. (2001) Beta-adrenergic receptor subtype-specific signaling in cardiac myocytes from beta(1) and beta(2) adrenoceptor knockout mice. Mol. Pharmacol. 60, 577–583.
Orita, H., Fukasawa, M., Hirooka, S., Uchino, H., Fukui, K., and Washio, M. (1993) Modulation of cardiac myocyte beating rate and hypertrophy by cardiac fibroblasts isolated from neonatal rat ventricle. Jpn Circ. J. 57, 912–920.
Kroll, M. H., Hellums, J. D., McIntire, L. V., Schafer, A. I., and Moake, J. L. (1996) Platelets and shear stress. Blood 88, 1525–1541.
Weinbaum, S., Cowin, S. C., and Zeng, Y. (1994) A model for the excitation of osteocytes by mechanical loading-induced bone fluid shear stresses. J. Biomech. 27, 339–360.
Schmid-Schonbein, G. W. (1999) Biomechanics of microcirculatory blood perfusion. Annu. Rev. Biomed. Eng. 1, 73–102.
Cohn, J. N. (1995) Critical review of heart failure: the role of left ventricular remodeling in the therapeutic response. Clin. Cardiol. 18, IV4-IV12.
Lodge, N. J., and Normandin, D. E. (1997) Alterations in Ito1, Ikr and Ik1 density in the BIO TO-2 strain of syrian myopathic hamsters. J. Mol. Cell. Cardiol. 29, 3211–3221.
Knollmann, B. C., Knollmann-Ritschel, B. E., Weissman, N. J., Jones, L. R., and Morad, M. (2000) Remodelling of ionic currents in hypertrophied and failing hearts of transgenic mice overexpressing calsequestrin. J. Physiol. 525, 483–498.
Janse, M. J. (2004) Electrophysiological changes in heart failure and their relationship to arrhythmogenesis. Cardiovasc. Res. 61, 208–217.
Cerbai, E., Barbieri, M., and Mugelli, A. (1994) Characterization of the hyperpolarization-activated current, I(f), in ventricular myocytes isolated from hypertensive rats. J. Physiol. 481, 585–591.
Reich, K. M., Gay, C. V., and Frangos, J. A. (1990) Fluid shear stress as a mediator of osteoblast cyclic adenosine monophosphate production. J. Cell. Physiol. 143, 100–104.
Bakker, A. D., Soejima, K., Klein-Nulend, J., and Burger, E. H. (2001) The production of nitric oxide and prostaglandin E(2) by primary bone cells is shear stress dependent. J. Biomech. 34, 671–677.
Slattery, M. J., Liang, S., and Dong, C. (2005) Distinct role of hydrodynamic sheart in leukocyte-facilitated tumor cell extravasation. Am. J. Physiol. Cell. Physiol. 288, C831-C839.
Reuter, H., Cachelin, A. B., De Peyer, J. E., and Kokubun, S. (1983) Modulation of calcium channels in cultured cardiac cells by isoproterenol and 8-bromo-cAMP. Cold Spring Harb. Symp. Quant. Biol. 48, 193–200.
Ross, R. S., and Borg, T. K. (2001) Integrins and the myocardium. Circ. Res. 88, 1112–1119.
Wang, Y. G., Samarel, A. M., and Lipsius, S. L. (2000) Laminin acts via beta 1 integrin signalling to alter cholinergic regulation of L-type Ca(2+) current in cat atrial myocytes. J. Physiol. 526, 57–68.
Cheng, Q., Ross, R. S., and Walsh, K. B. (2004) Overexpression of the integrin beta(1A) subunit and the beta(1A) cytoplasmic domain modifies the beta-adrenergic regulation of the cardiac L-type Ca(2+) current. J. Mol. Cell. Cardiol. 36, 809–819.
Communal, C., Singh, M., Menon, B., Xie, Z., Colucci, W. S., and Singh, K. (2003) beta1 integrins expression in adult rat ventricular myocytes and its role in the regulation of beta-adrenergic receptor-stimulated apoptosis. J. Cell. Biochem. 89, 381–8.
Wang, Y. G., Samarel, A. M., and Lipsius, S. L. (2000) Laminin binding to beta1-integrins selectively alters beta1- and beta2-adrenoceptor signalling in cat atrial myocytes. J. Physiol. 527, 3–9.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Lorenzen-Schmidt, I., Schmid-Schönbein, G.W., Giles, W.R. et al. Chronotropic response of cultured neonatal rat ventricular myocytes to short-term fluid shear. Cell Biochem Biophys 46, 113–122 (2006). https://doi.org/10.1385/CBB:46:2:113
Issue Date:
DOI: https://doi.org/10.1385/CBB:46:2:113