0
Review Article

Molecular Mechanisms for the Mechanical Modulation of Airway Responsiveness

[+] Author and Article Information
Wenwu Zhang

Department of Cellular and
Integrative Physiology,
Indiana University School of Medicine,
Indianapolis, IN 46202

Susan J. Gunst

Department of Cellular and
Integrative Physiology,
Indiana University School of Medicine,
Indianapolis, IN 46202
e-mail: Sgunst@iupui.edu

1Corresponding author.

Manuscript received September 25, 2018; final manuscript received January 15, 2019; published online February 19, 2019. Assoc. Editor: Chun Seow.

ASME J of Medical Diagnostics 2(1), 010805 (Feb 19, 2019) (8 pages) Paper No: JESMDT-18-1053; doi: 10.1115/1.4042775 History: Received September 25, 2018; Revised January 15, 2019

The smooth muscle of the airways is exposed to continuously changing mechanical forces during normal breathing. The mechanical oscillations that occur during breathing have profound effects on airway tone and airway responsiveness both in experimental animals and humans in vivo and in isolated airway tissues in vitro. Experimental evidence suggests that alterations in the contractile and mechanical properties of airway smooth muscle tissues caused by mechanical perturbations result from adaptive changes in the organization of the cytoskeletal architecture of the smooth muscle cell. The cytoskeleton is a dynamic structure that undergoes rapid reorganization in response to external mechanical and pharmacologic stimuli. Contractile stimulation initiates the assembly of cytoskeletal/extracellular matrix adhesion complex proteins into large macromolecular signaling complexes (adhesomes) that undergo activation to mediate the polymerization and reorganization of a submembranous network of actin filaments at the cortex of the cell. Cortical actin polymerization is catalyzed by Neuronal-Wiskott–Aldrich syndrome protein (N-WASP) and the Arp2/3 complex, which are activated by pathways regulated by paxillin and the small GTPase, cdc42. These processes create a strong and rigid cytoskeletal framework that may serve to strengthen the membrane for the transmission of force generated by the contractile apparatus to the extracellular matrix, and to enable the adaptation of smooth muscle cells to mechanical stresses. This model for the regulation of airway smooth muscle function can provide novel perspectives to explain the normal physiologic behavior of the airways and pathophysiologic properties of the airways in asthma.

FIGURES IN THIS ARTICLE
<>
Copyright © 2019 by ASME
Your Session has timed out. Please sign back in to continue.

References

Fish, J. E. , Ankin, M. G. , Kelly, J. F. , and Peterman, V. I. , 1981, “ Regulation of Bronchomotor Tone by Lung Inflation in Asthmatic and Nonasthmatic Subjects,” J. Appl. Physiol., 50(5), pp. 1079–1086. [CrossRef]
Gunst, S. J. , Shen, X. , and Tepper, R. S. , 2001, “ Bronchoprotective and Bronchodilatory Effects of Deep Inspiration in Rabbits Subjected to Methacholine Challenge,” J. Appl. Physiol., 91(6), pp. 2511–2516. [CrossRef] [PubMed]
Kapsali, T. , Permutt, S. , Laube, B. , Scichilone, N. , and Togias, A. , 2000, “ Potent Bronchoprotective Effect of Deep Inspiration and Its Absence in Asthma,” J. Appl. Physiol., 89(2), pp. 711–720. [CrossRef] [PubMed]
King, G. G. , Moore, B. J. , Seow, C. Y. , and Pare, P. D. , 1999, “ Time Course of Increased Airway Narrowing Caused by Inhibition of Deep Inspiration During Methacholine Challenge,” Am. J. Respir. Crit. Care Med., 160(2), pp. 454–457. [CrossRef] [PubMed]
Nadel, J. A. , and Tierney, D. F. , 1961, “ Effect of a Previous Deep Inspiration on Airway Resistance in Man,” J. Appl. Physiol., 16, pp. 717–719. [CrossRef] [PubMed]
Shinozuka, N. , Lavoie, J. P. , Martin, J. G. , and Bates, J. H. , 1998, “ Effect of Time-Varying Load on Degree of Bronchoconstriction in the Dog,” J. Appl. Physiol., 85(4), pp. 1464–1470. [CrossRef] [PubMed]
Warner, D. O. , and Gunst, S. J. , 1992, “ Limitation of Maximal Bronchoconstriction in Living Dogs,” Am. Rev. Respir. Dis., 145(3), pp. 553–560. [CrossRef] [PubMed]
Skloot, G. , Permutt, S. , and Togias, A. , 1995, “ Airway Hyperresponsiveness in Asthma: A Problem of Limited Smooth Muscle Relaxation With Inspiration,” J. Clin. Invest., 96(5), pp. 2393–2403. [CrossRef] [PubMed]
An, S. S. , Bai, T. R. , Bates, J. H. , Black, J. L. , Brown, R. H. , Brusasco, V. , Chitano, P. , Deng, L. , Dowell, M. , Eidelman, D. H. , Fabry, B. , Fairbank, N. J. , Ford, L. E. , Fredberg, J. J. , Gerthoffer, W. T. , Gilbert, S. H. , Gosens, R. , Gunst, S. J. , Halayko, A. J. , Ingram, R. H. , Irvin, C. G. , James, A. L. , Janssen, L. J. , King, G. G. , Knight, D. A. , Lauzon, A. M. , Lakser, O. J. , Ludwig, M. S. , Lutchen, K. R. , Maksym, G. N. , Martin, J. G. , Mauad, T. , McParland, B. E. , Mijailovich, S. M. , Mitchell, H. W. , Mitchell, R. W. , Mitzner, W. , Murphy, T. M. , Pare, P. D. , Pellegrino, R. , Sanderson, M. J. , Schellenberg, R. R. , Seow, C. Y. , Silveira, P. S. , Smith, P. G. , Solway, J. , Stephens, N. L. , Sterk, P. J. , Stewart, A. G. , Tang, D. D. , Tepper, R. S. , Tran, T. , and Wang, L. , 2007, “ Airway Smooth Muscle Dynamics: A Common Pathway of Airway Obstruction in Asthma,” Eur. Respir. J., 29(5), pp. 834–860. [CrossRef] [PubMed]
King, G. G. , Moore, B. J. , and Pare, P. D. , 1998, “ The Time Course of Excessive Airway Narrowing Caused by Inhibition of Deep Inspirations During Bronchoconstriction in Normal Subjects,” Am. J. Respir. Crit. Med., 157(2), p. A515.
Shen, X. , Gunst, S. J. , and Tepper, R. S. , 1997, “ Effect of Tidal Volume and Frequency on Airway Responsiveness in Mechanically Ventilated Rabbits,” J. Appl. Physiol., 83(4), pp. 1202–1208. [CrossRef] [PubMed]
Brusasco, V. , Crimi, E. , Barisione, G. , Spanevello, A. , Rodarte, J. R. , and Pellegrino, R. , 1999, “ Airway Responsiveness to Methacholine: Effects of Deep Inhalations and Airway Inflammation,” J. Appl. Physiol., 87(2), pp. 567–573. [CrossRef] [PubMed]
Gunst, S. J. , Stropp, J. Q. , and Service, J. , 1990, “ Mechanical Modulation of Pressure-Volume Characteristics of Contracted Canine Airways In Vitro,” J. Appl. Physiol., 68(5), pp. 2223–2229. [CrossRef] [PubMed]
Desai, L. P. , Wu, Y. , Tepper, R. S. , and Gunst, S. J. , 2011, “ Mechanical Stimuli and IL-13 Interact at Integrin Adhesion Complexes to Regulate Expression of Smooth Muscle Myosin Heavy Chain in Airway Smooth Muscle Tissue,” Am. J. Physiol. Lung Cell Mol. Physiol., 301(3), pp. L275–L284. [CrossRef] [PubMed]
Wu, Y. , Huang, Y. , and Gunst, S. J. , 2016, “ Focal Adhesion Kinase (FAK) and Mechanical Stimulation Negatively Regulate the Transition of Airway Smooth Muscle Tissues to a Synthetic Phenotype,” Am. J. Physiol. Lung Cell Mol. Physiol., 311(5), pp. L893–L902. [CrossRef] [PubMed]
Xue, Z. , Yu, Y. , Gao, H. , Gunst, S. J. , and Tepper, R. S. , 2011, “ Chronic Continuous Positive Airway Pressure (CPAP) Reduces Airway Reactivity In Vivo in an Allergen-Induced Rabbit Model of Asthma,” J. Appl. Physiol., 111(2), pp. 353–357. [CrossRef] [PubMed]
Xue, Z. , Zhang, W. , Desai, L. P. , Gao, H. , Gunst, S. J. , and Tepper, R. S. , 2013, “ Increased Mechanical Strain Imposed on Murine Lungs During Ventilation In Vivo Depresses Airway Responsiveness and Activation of Protein Kinase AKT1,” J. Appl. Physiol., 114(11), pp. 1506–1510. [CrossRef] [PubMed]
Gunst, S. J. , Meiss, R. A. , Wu, M. F. , and Rowe, M. , 1995, “ Mechanisms for the Mechanical Plasticity of Tracheal Smooth Muscle,” Am. J. Physiol., 268(5 Pt. 1), pp. C1267–C1276. [CrossRef] [PubMed]
Shen, X. , Wu, M. F. , Tepper, R. S. , and Gunst, S. J. , 1997, “ Pharmacological Modulation of the Mechanical Response of Airway Smooth Muscle to Length Oscillation,” J. Appl. Physiol., 83(3), pp. 739–745. [CrossRef] [PubMed]
Shen, X. , Wu, M. F. , Tepper, R. S. , and Gunst, S. J. , 1997, “ Mechanisms for the Mechanical Response of Airway Smooth Muscle to Length Oscillation,” J. Appl. Physiol., 83(3), pp. 731–738. [CrossRef] [PubMed]
Gunst, S. J. , and Wu, M. F. , 2001, “ Plasticity of Airway Smooth Muscle Stiffness and Extensibility: Role of Length-Adaptive Mechanisms,” J. Appl. Physiol., 90(2), pp. 741–749. [CrossRef] [PubMed]
Gunst, S. J. , 2002, “ Role of Airway Smooth Muscle Mechanical Properties in the Regulation of Airway Caliber,” Mechanics of Breathing: Pathophysiology, Diagnosis and Treatment, A. Alverti , ed., Springer-Verlag, Milan, Italy, pp. 34–44.
Gunst, S. J. , 1983, “ Contractile Force of Canine Airway Smooth Muscle During Cyclical Length Changes,” J. Appl. Physiol.: Respir. Environ. Exercise. Physiol., 55(3), pp. 759–769.
Gunst, S. J. , and Mitzner, W. , 1981, “ Mechanical Properties of Contracted Canine Bronchial Segments In Vitro,” J. Appl. Physiol.: Respir. Environ. Exercise Physiol., 50(6), pp. 1236–1247.
Fredberg, J. J. , Inouye, D. , Miller, B. , Nathan, M. , Jafari, S. , Raboudi, S. H. , Butler, J. P. , and Shore, S. A. , 1997, “ Airway Smooth Muscle, Tidal Stretches, and Dynamically Determined Contractile States,” Am. J. Respir. Crit. Care Med., 156(6), pp. 1752–1759. [CrossRef] [PubMed]
Wang, L. , Pare, P. D. , and Seow, C. Y. , 2000, “ Effects of Length Oscillation on the Subsequent Force Development in Swine Tracheal Smooth Muscle,” J. Appl. Physiol., 88(6), pp. 2246–2250. [CrossRef] [PubMed]
Pascoe, C. D. , Donovan, G. M. , Bosse, Y. , Seow, C. Y. , and Pare, P. D. , 2014, “ Bronchoprotective Effect of Simulated Deep Inspirations in Tracheal Smooth Muscle,” J. Appl. Physiol., 117(12), pp. 1502–1513. [CrossRef] [PubMed]
Mehta, D. , Wu, M. F. , and Gunst, S. J. , 1996, “ Role of Contractile Protein Activation in the Length-Dependent Modulation of Tracheal Smooth Muscle Force,” Am. J. Physiol., 270(1), pp. C243–252. [CrossRef] [PubMed]
Bai, T. R. , Bates, J. H. , Brusasco, V. , Camoretti-Mercado, B. , Chitano, P. , Deng, L. H. , Dowell, M. , Fabry, B. , Ford, L. E. , Fredberg, J. J. , Gerthoffer, W. T. , Gilbert, S. H. , Gunst, S. J. , Hai, C. M. , Halayko, A. J. , Hirst, S. J. , James, A. L. , Janssen, L. J. , Jones, K. A. , King, G. G. , Lakser, O. J. , Lambert, R. K. , Lauzon, A. M. , Lutchen, K. R. , Maksym, G. N. , Meiss, R. A. , Mijailovich, S. M. , Mitchell, H. W. , Mitchell, R. W. , Mitzner, W. , Murphy, T. M. , Pare, P. D. , Schellenberg, R. R. , Seow, C. Y. , Sieck, G. C. , Smith, P. G. , Smolensky, A. V. , Solway, J. , Stephens, N. L. , Stewart, A. G. , Tang, D. D. , and Wang, L. , 2004, “ On the Terminology for Describing the Length-Force Relationship and Its Changes in Airway Smooth Muscle,” J. Appl. Physiol., 97(6), pp. 2029–2034. [CrossRef] [PubMed]
Ford, L. E. , Seow, C. Y. , and Pratusevich, V. R. , 1994, “ Plasticity in Smooth Muscle, a Hypothesis,” Can. J. Physiol. Pharmacol., 72(11), pp. 1320–1324. [CrossRef] [PubMed]
Gunst, S. J. , and Tang, D. D. , 2000, “ The Contractile Apparatus and Mechanical Properties of Airway Smooth Muscle,” Eur. Respir. J., 15(3), pp. 600–616. [CrossRef] [PubMed]
Pratusevich, V. R. , Seow, C. Y. , and Ford, L. E. , 1995, “ Plasticity in Canine Airway Smooth Muscle,” J. Gen. Physiol., 105(1), pp. 73–94. [CrossRef] [PubMed]
Gunst, S. J. , and Russell, J. A. , 1982, “ Contractile Force of Canine Tracheal Smooth Muscle During Continuous Stretch,” J. Appl. Physiol.: Respir. Environ. Exercise Physiol., 52(3), pp. 655–663.
Gunst, S. J. , 1986, “ Effect of Length History on Contractile Behavior of Canine Tracheal Smooth Muscle,” Am. J. Physiol., 250(1), pp. C146–C154. [CrossRef] [PubMed]
Gunst, S. J. , Wu, M. F. , and Smith, D. D. , 1993, “ Contraction History Modulates Isotonic Shortening Velocity in Smooth Muscle,” Am. J. Physiol., 265(2), pp. C467–476. [CrossRef] [PubMed]
Stephens, N. L. , and Van Niekerk, W. , 1977, “ Isometric and Isotonic Contractions in Airway Smooth Muscle,” Can. J. Physiol. Pharmacol., 55(4), pp. 833–838. [CrossRef] [PubMed]
Chan, W. L. , Silberstein, J. , and Hai, C. M. , 2000, “ Mechanical Strain Memory in Airway Smooth Muscle,” Am. J. Physiol. Cell Physiol., 278(5), pp. C895–C904. [CrossRef] [PubMed]
Meiss, R. A. , 1993, “ Persistent Mechanical Effects of Decreasing Length During Isometric Contraction of Ovarian Ligament Smooth Muscle,” J. Muscle Res. Cell Motil., 14(2), pp. 205–218. [CrossRef] [PubMed]
Harris, D. E. , and Warshaw, D. M. , 1991, “ Length vs. Active Force Relationship in Single Isolated Smooth Muscle Cells,” Am. J. Physiol., 260(5), pp. C1104–C1112. [CrossRef] [PubMed]
An, S. S. , Laudadio, R. E. , Lai, J. , Rogers, R. A. , and Fredberg, J. J. , 2002, “ Stiffness Changes in Cultured Airway Smooth Muscle Cells,” Am. J. Physiol. Cell Physiol., 283(3), pp. C792–C801. [CrossRef] [PubMed]
Gunst, S. J. , Tang, D. D. , and Opazo, S. A. , 2003, “ Cytoskeletal Remodeling of the Airway Smooth Muscle Cell: A Mechanism for Adaptation to Mechanical Forces in the Lung,” Respir. Physiol. Neurobiol., 137(2–3), pp. 151–168. [CrossRef] [PubMed]
Gunst, S. J. , and Zhang, W. , 2008, “ Actin Cytoskeletal Dynamics in Smooth Muscle: A New Paradigm for the Regulation of Smooth Muscle Contraction,” Am. J. Physiol. Cell. Physiol., 295(3), pp. C576–C587. [CrossRef] [PubMed]
Zhang, W. , and Gunst, S. J. , 2008, “ Dynamics of Cytoskeletal and Contractile Protein Organization: An Emerging Paradigm for Airway Smooth Muscle Contraction,” Airway Smooth Muscle Biology and Pharmacology, K. F. Chung , ed., Wiley Press, Hoboken, NJ.
Opazo Saez, A. , Zhang, W. , Wu, Y. , Turner, C. E. , Tang, D. D. , and Gunst, S. J. , 2004, “ Tension Development During Contractile Stimulation of Smooth Muscle Requires Recruitment of Paxillin and Vinculin to the Membrane,” Am. J. Physiol Cell Physiol., 286(2), pp. C433–C447. [CrossRef] [PubMed]
Zhang, W. , Huang, Y. , Wu, Y. , and Gunst, S. J. , 2015, “ A Novel Role for RhoA GTPase in the Regulation of Airway Smooth Muscle Contraction,” Can. J. Physiol. Pharmacol., 93(2), pp. 129–136. [CrossRef] [PubMed]
Zhang, W. , Huang, Y. , and Gunst, S. J. , 2012, “ The Small GTPase RhoA Regulates the Contraction of Smooth Muscle Tissues by Catalyzing the Assembly of Cytoskeletal Signaling Complexes at Membrane Adhesion Sites,” J. Biol. Chem., 287(41), pp. 33996–34008. [CrossRef] [PubMed]
Huang, Y. , Zhang, W. , and Gunst, S. J. , 2011, “ Activation of Vinculin Induced by Cholinergic Stimulation Regulates Contraction of Tracheal Smooth Muscle Tissue,” J. Biol. Chem., 286(5), pp. 3630–3644. [CrossRef] [PubMed]
Wang, N. , Butler, J. P. , and Ingber, D. E. , 1993, “ Mechanotransduction Across the Cell Surface and Through the Cytoskeleton,” Science, 260(5111), pp. 1124–1127. [CrossRef] [PubMed]
Wang, N. , and Ingber, D. E. , 1994, “ Control of Cytoskeletal Mechanics by Extracellular Matrix, Cell Shape, and Mechanical Tension,” Biophys. J., 66(6), pp. 2181–2189. [CrossRef] [PubMed]
Shyy, J. Y. , and Chien, S. , 1997, “ Role of Integrins in Cellular Responses to Mechanical Stress and Adhesion,” Curr. Opin. Cell. Biol., 9(5), pp. 707–713. [CrossRef] [PubMed]
Wu, Y. , Huang, Y. , Herring, B. P. , and Gunst, S. J. , 2008, “ Integrin-Linked Kinase Regulates Smooth Muscle Differentiation Marker Gene Expression in Airway Tissue,” Am. J. Physiol. Lung Cell Mol. Physiol., 295(6), pp. L988–L997. [CrossRef] [PubMed]
Zhang, W. , and Gunst, S. J. , 2017, “ Non-Muscle (NM) Myosin Heavy Chain Phosphorylation Regulates the Formation of NM Myosin Filaments, Adhesome Assembly and Smooth Muscle Contraction,” J. Physiol., 595(13), pp. 4279–4300. [CrossRef] [PubMed]
Qi, D. , Mitchell, R. W. , Burdyga, T. , Ford, L. E. , Kuo, K. H. , and Seow, C. Y. , 2002, “ Myosin Light Chain Phosphorylation Facilitates In Vivo Myosin Filament Reassembly After Mechanical Perturbation,” Am. J. Physiol. Cell Physiol., 282(6), pp. C1298–C1305. [CrossRef] [PubMed]
Xu, J. Q. , Gillis, J. M. , and Craig, R. , 1997, “ Polymerization of Myosin on Activation of Rat Anococcygeus Smooth Muscle,” J. Muscle Res. Cell Motil., 18(3), pp. 381–393. [CrossRef] [PubMed]
Seow, C. Y. , 2005, “ Myosin Filament Assembly in an Ever-Changing Myofilament Lattice of Smooth Muscle,” Am. J. Physiol. Cell Physiol., 289(6), pp. C1363–C1368. [CrossRef] [PubMed]
Lan, B. , Deng, L. , Donovan, G. M. , Chin, L. Y. , Syyong, H. T. , Wang, L. , Zhang, J. , Pascoe, C. D. , Norris, B. A. , Liu, J. C. , Swyngedouw, N. E. , Banaem, S. M. , Pare, P. D. , and Seow, C. Y. , 2015, “ Force Maintenance and Myosin Filament Assembly Regulated by Rho-Kinase in Airway Smooth Muscle,” Am. J. Physiol. Lung Cell Mol. Physiol., 308(1), pp. L1–L10. [CrossRef] [PubMed]
Chitano, P. , Wang, L. , Tin, G. Y. Y. , Ikebe, M. , Pare, P. D. , and Seow, C. Y. , 2017, “ Smooth Muscle Function and Myosin Polymerization,” J. Cell Sci., 130(15), pp. 2468–2480. [CrossRef] [PubMed]
Herrera, A. M. , Martinez, E. C. , and Seow, C. Y. , 2004, “ Electron Microscopic Study of Actin Polymerization in Airway Smooth Muscle,” Am. J. Physiol. Lung Cell Mol. Physiol., 286(6), pp. L1161–L1168. [CrossRef] [PubMed]
Murphy, R. A. , 1982, “ Myosin Phosphorylation and Crossbridge Regulation in Arterial Smooth Muscle: State-or-the-Art Review,” Hypertension, 4(3 Pt. 2), pp. 3–7. [PubMed]
Stull, J. T. , Hsu, L. C. , Tansey, M. G. , and Kamm, K. E. , 1990, “ Myosin Light Chain Kinase Phosphorylation in Tracheal Smooth Muscle,” J. Biol. Chem., 265(27), pp. 16683–16690. [PubMed]
Ito, M. , and Hartshorne, D. J. , 1990, “ Phosphorylation of Myosin as a Regulatory Mechanism in Smooth Muscle,” Prog. Clin. Biol. Res., 327(1), pp. 57–72. [PubMed]
Pfitzer, G. , 2001, “ Invited Review: Regulation of Myosin Phosphorylation in Smooth Muscle,” J. Appl. Physiol., 91(1), pp. 497–503. [CrossRef] [PubMed]
Mehta, D. , and Gunst, S. J. , 1999, “ Actin Polymerization Stimulated by Contractile Activation Regulates Force Development in Canine Tracheal Smooth Muscle,” J. Physiol., 519(3), pp. 829–840. [CrossRef] [PubMed]
Cipolla, M. J. , Gokina, N. I. , and Osol, G. , 2002, “ Pressure-Induced Actin Polymerization in Vascular Smooth Muscle as a Mechanism Underlying Myogenic Behavior,” FASEB J., 16(1), pp. 72–76. [CrossRef] [PubMed]
Jones, K. A. , Perkins, W. J. , Lorenz, R. R. , Prakash, Y. S. , Sieck, G. C. , and Warner, D. O. , 1999, “ F-Actin Stabilization Increases Tension Cost During Contraction of Permeabilized Airway Smooth Muscle in Dogs,” J. Physiol., 519(2), pp. 527–538. [CrossRef] [PubMed]
Kim, H. R. , Gallant, C. , Leavis, P. C. , Gunst, S. J. , and Morgan, K. G. , 2008, “ Cytoskeletal Remodeling in Differentiated Vascular Smooth Muscle Is Actin Isoform-Dependent and Stimulus-Dependent,” Am. J. Physiol. Cell Physiol., 295(3), pp. C768–C778. [CrossRef] [PubMed]
Tang, D. D. , and Gunst, S. J. , 2004, “ The Small GTPase cdc42 Regulates Actin Polymerization and Tension Development During Contractile Stimulation of Smooth Muscle,” J. Biol. Chem., 279(50), pp. 51722–51728. [CrossRef] [PubMed]
Tang, D. D. , and Tan, J. , 2003, “ Downregulation of Profilin With Antisense Oligodeoxynucleotides Inhibits Force Development During Stimulation of Smooth Muscle,” Am. J. Physiol. Heart Circ. Physiol., 285(4), pp. H1528–H1536. [CrossRef] [PubMed]
Tang, D. D. , Zhang, W. , and Gunst, S. J. , 2005, “ The Adapter Protein CrkII Regulates Neuronal Wiskott-Aldrich Syndrome Protein, Actin Polymerization, and Tension Development During Contractile Stimulation of Smooth Muscle,” J. Biol. Chem., 280(24), pp. 23380–23389. [CrossRef] [PubMed]
Walsh, M. P. , and Cole, W. C. , 2013, “ The Role of Actin Filament Dynamics in the Myogenic Response of Cerebral Resistance Arteries,” J. Cereb. Blood Flow Metab., 33(1), pp. 1–12. [CrossRef] [PubMed]
Zhang, W. , Du, L. , and Gunst, S. J. , 2010, “ The Effects of the Small GTPase RhoA on the Muscarinic Contraction of Airway Smooth Muscle Result From Its Role in Regulating Actin Polymerization,” Am. J. Physiol. Cell Physiol., 299(2), pp. C298–C306. [CrossRef] [PubMed]
Zhang, W. , Huang, Y. , and Gunst, S. J. , 2016, “ p21-Activated Kinase (Pak) Regulates Airway Smooth Muscle Contraction by Regulating Paxillin Complexes That Mediate Actin Polymerization,” J. Physiol., 594(17), pp. 4879–4900. [CrossRef] [PubMed]
Zhang, W. , Wu, Y. , Wu, C. , and Gunst, S. J. , 2007, “ Integrin-Linked Kinase (ILK) Regulates N-WASp-Mediated Actin Polymerization and Tension Development in Tracheal Smooth Muscle,” J. Biol. Chem., 282(47), pp. 34568–34580. [CrossRef] [PubMed]
Zhao, R. , Du, L. , Huang, Y. , Wu, Y. , and Gunst, S. J. , 2008, “ ADF/Cofilin Activation Regulates Actin Polymerization and Tension Development in Canine Tracheal Smooth Muscle,” J. Biol. Chem., 283(52), pp. 36522–36531. [CrossRef] [PubMed]
Zhang, W. , Wu, Y. , Du, L. , Tang, D. D. , and Gunst, S. J. , 2005, “ Activation of the Arp2/3 Complex by N-WASp Is Required for Actin Polymerization and Contraction in Smooth Muscle,” Am. J. Physiol. Cell Physiol., 288(5), pp. C1145–C1160. [CrossRef] [PubMed]
Barany, M. , Barron, J. T. , Gu, L. , and Barany, K. , 2001, “ Exchange of the Actin-Bound Nucleotide in Intact Arterial Smooth Muscle,” J. Biol. Chem., 276(51), pp. 48398–48403. [CrossRef] [PubMed]
Rembold, C. M. , Tejani, A. D. , Ripley, M. L. , and Han, S. , 2007, “ Paxillin Phosphorylation, Actin Polymerization, Noise Temperature, and the Sustained Phase of Swine Carotid Artery Contraction,” Am. J. Physiol. Cell Physiol., 293(3), pp. C993–1002. [CrossRef] [PubMed]
Tejani, A. D. , and Rembold, C. M. , 2010, “ Force Augmentation and Stimulated Actin Polymerization in Swine Carotid Artery,” Am. J. Physiol. Cell Physiol., 298(1), pp. C182–C190. [CrossRef] [PubMed]
Corteling, R. L. , Brett, S. E. , Yin, H. , Zheng, X. L. , Walsh, M. P. , and Welsh, D. G. , 2007, “ The Functional Consequence of RhoA Knockdown by RNA Interference in Rat Cerebral Arteries,” Am. J. Physiol. Heart Circ. Physiol., 293(1), pp. H440–H447. [CrossRef] [PubMed]
Zhang, W. , and Gunst, S. J. , 2008, “ Interactions of Airway Smooth Muscle Cells With Their Tissue Matrix: Implications for Contraction,” Proc. Am. Thorac. Soc., 5(1), pp. 32–39. [CrossRef] [PubMed]
Huang, Y. , Day, R. N. , and Gunst, S. J. , 2014, “ Vinculin Phosphorylation at Tyr1065 Regulates Vinculin Conformation and Tension Development in Airway Smooth Muscle Tissues,” J. Biol. Chem., 289(6), pp. 3677–3688. [CrossRef] [PubMed]
Higgs, H. N. , and Pollard, T. D. , 2001, “ Regulation of Actin Filament Network Formation Through ARP2/3 Complex: Activation by a Diverse Array of Proteins,” Annu. Rev. Biochem., 70(1), pp. 649–676. [CrossRef] [PubMed]
Mullins, R. D. , 2000, “ How WASP-Family Proteins and the ARP2/3 Complex Convert Intracellular Signals Into Cytoskeletal Structures,” Curr. Opin. Cell Biol., 12(1), pp. 91–96. [PubMed]
Rohatgi, R. , Ma, L. , Miki, H. , Lopez, M. , Kirchhausen, T. , Takenawa, T. , and Kirschner, M. W. , 1999, “ The Interaction Between N-WASP and the ARP2/3 Complex Links cdc42-Dependent Signals to Actin Assembly,” Cell, 97(2), pp. 221–231. [PubMed]
Higgs, H. N. , and Pollard, T. D. , 2000, “ Activation by cdc42 and PIP2 of Wiskott-Aldrich Syndrome Protein (Wasp) Stimulates Actin Nucleation by Arp2/3 Complex,” J. Cell Biol., 150(6), pp. 1311–1320. [PubMed]
Rohatgi, R. , Ho, H. Y. , and Kirschner, M. W. , 2000, “ Mechanism of N-WASP Activation by cdc42 and Phosphatidylinositol 4, 5-Bisphosphate,” J. Cell Biol., 150(6), pp. 1299–1310. [PubMed]
Burridge, K. , and Chrzanowska-Wodnicka, M. , 1996, “ Focal Adhesions, Contractility, and Signaling,” Annu. Rev. Cell Dev. Biol., 12, pp. 463–518. [PubMed]
Coppolino, M. G. , and Dedhar, S. , 2000, “ Bi-Directional Signal Transduction by Integrin Receptors,” Int. J. Biochem. Cell Biol., 32(2), pp. 171–188. [PubMed]
Critchley, D. R. , Holt, M. R. , Barry, S. T. , Priddle, H. , Hemmings, L. , and Norman, J. , 1999, “ Integrin-Mediated Cell Adhesion: The Cytoskeletal Connection,” Biochem. Soc. Symp., 65(1), pp. 79–99. [PubMed]
Schmidt, C. , Pommerenke, H. , Durr, F. , Nebe, B. , and Rychly, J. , 1998, “ Mechanical Stressing of Integrin Receptors Induces Enhanced Tyrosine Phosphorylation of Cytoskeletally Anchored Proteins,” J. Biol. Chem., 273(9), pp. 5081–5085. [PubMed]
Zhang, W. W. , and Gunst, S. J. , 2006, “ Dynamic Association Between Alpha-Actinin and Beta-Integrin Regulates Contraction of Canine Tracheal Smooth Muscle,” J. Physiol.-London, 572(3), pp. 659–676.
Wang, Z. , Pavalko, F. M. , and Gunst, S. J. , 1996, “ Tyrosine Phosphorylation of the Dense Plaque Protein Paxillin Is Regulated During Smooth Muscle Contraction,” Am. J. Physiol., 271(5), pp. C1594–C1602. [PubMed]
Tang, D. D. , Turner, C. E. , and Gunst, S. J. , 2003, “ Expression of Non-Phosphorylatable Paxillin Mutants in Canine Tracheal Smooth Muscle Inhibits Tension Development,” J. Physiol., 553(1), pp. 21–35. [PubMed]
Tang, D. D. , and Gunst, S. J. , 2001, “ Depletion of Focal Adhesion Kinase by Antisense Depresses Contractile Activation of Smooth Muscle,” Am. J. Physiol. Cell Physiol., 280(4), pp. C874–C883. [PubMed]
Tang, D. D. , and Gunst, S. J. , 2001, “ Selected Contribution: Roles of Focal Adhesion Kinase and Paxillin in the Mechanosensitive Regulation of Myosin Phosphorylation in Smooth Muscle,” J. Appl. Physiol., 91(3), pp. 1452–1459. [PubMed]
Kuo, K. H. , and Seow, C. Y. , 2004, “ Contractile Filament Architecture and Force Transmission in Swine Airway Smooth Muscle,” J. Cell Sci., 117(8), pp. 1503–1511. [PubMed]
Lan, B. , Norris, B. A. , Liu, J. C. , Pare, P. D. , Seow, C. Y. , and Deng, L. , 2015, “ Development and Maintenance of Force and Stiffness in Airway Smooth Muscle,” Can. J. Physiol. Pharmacol., 93(3), pp. 163–169. [PubMed]
Cremo, C. , and Harteshorne, D. J. , 2008, Myosins: A Superfamily of Molecular Motors, L. M. Coluccio , Springer, Dordrecht, The Netherlands, pp. 171–222.
Vicente-Manzanares, M. , Ma, X. , Adelstein, R. S. , and Horwitz, A. R. , 2009, “ Non-Muscle Myosin II Takes Centre Stage in Cell Adhesion and Migration,” Nat. Rev. Mol. Cell Biol., 10(11), pp. 778–790. [PubMed]
Milton, D. L. , Schneck, A. N. , Ziech, D. A. , Ba, M. , Facemyer, K. C. , Halayko, A. J. , Baker, J. E. , Gerthoffer, W. T. , and Cremo, C. R. , 2011, “ Direct Evidence for Functional Smooth Muscle Myosin II in the 10S Self-Inhibited Monomeric Conformation in Airway Smooth Muscle Cells,” Proc. Natl. Acad. Sci. U. S. A, 108(4), pp. 1421–1426. [PubMed]

Figures

Grahic Jump Location
Fig. 1

The volume of tidal breath oscillations regulates airway dilation and airway caliber in anesthetized rabbits. Airway resistance (Raw) versus time from initiation of challenge with intravenous methacholine (MCh; 0.01 mg/kg) at different volumes of tidal ventilation. Modified from Shen et al. [11].

Grahic Jump Location
Fig. 2

Increasing the amplitude of tidal volume oscillations reduces the magnitude of the transmural pressure of isolated canine intraparenchymal bronchi contracted with acetylcholine. Modified from Gunst et al. [13].

Grahic Jump Location
Fig. 3

Tracheal muscle tissues strips were subjected to length steps either before (a) or after 1 min of contractile stimulation with ACh (b). Force in response to ACh was much higher when the length step was performed prior to contractile stimulation than when the length step occurred during contractile stimulation. Modified from Gunst et al. [18].

Grahic Jump Location
Fig. 4

Smooth muscle cell cytoskeletal structure and organization. (a). Actin filaments within the contractile apparatus and at the cell cortex linked to integrin proteins at membrane adhesion junctions that connect to the extracellular matrix. (b) Molecular organization of integrin-associated adhesome complexes in smooth muscle cells.

Grahic Jump Location
Fig. 5

(a) Model of smooth muscle shortening and tension development. Contractile and mechanical stimuli induce the recruitment of cytoskeletal signaling proteins to membrane adhesion sites and cortical actin polymerization. (b) Signals pathways regulated by integrin receptors and G protein-coupled receptors (GPCR) collaborate to regulate tension development in airway smooth muscle. Both pathways are necessary for tension development.

Grahic Jump Location
Fig. 6

Molecular mechanism for the assembly of adhesome complexes in airway smooth muscle: (1) ACh stimulation activates RhoA, which regulates regulatory light chain phosphorylation of NM myosin and the assembly and activation of NM myosin II. (2) Activated NM actomyosin mediates the recruitment of inactive proteins to membrane adhesome complexes, where they undergo activation to regulate cytoskeletal signaling pathways. (3) Cdc42 activates N-WASp and the Arp2/3 complex, which catalyzes cortical actin polymerization. Signals from G-protein coupled receptors (GPCR) activate MLC kinase which regulates SM myosin regulatory light chain phosphorylation and the activation of SM myosin crossbridge cycling.

Tables

Errata

Some tools below are only available to our subscribers or users with an online account.

Related Content

Customize your page view by dragging and repositioning the boxes below.

Related Journal Articles
Related eBook Content
Topic Collections

Sorry! You do not have access to this content. For assistance or to subscribe, please contact us:

  • TELEPHONE: 1-800-843-2763 (Toll-free in the USA)
  • EMAIL: asmedigitalcollection@asme.org
Sign In