Circulation Research. 2003;93:548-556
Published online before print August 14, 2003, doi: 10.1161/01.RES.0000090998.08629.60
Published online before print August 14, 2003, doi: 10.1161/01.RES.0000090998.08629.60
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
© 2003 American Heart Association, Inc.
Cellular Biology |
Ca2+-Dependent Activation of Rho and Rho Kinase in Membrane Depolarization–Induced and Receptor Stimulation–Induced Vascular Smooth Muscle Contraction
From the Department of Physiology (S.S., N.T., N.S., Y.W., Y.T.), Kanazawa University Graduate School of Medicine, Kanazawa, Japan; Asahi Chemical Industry (M.S.), Fuji, Japan; and Department of Pharmacology (Y.S.), Kitazato University School of Pharmaceutical Sciences, Tokyo, Japan.
Correspondence to Yoh Takuwa, MD, Department of Physiology, Kanazawa University Graduate School of Medicine, 13-1 Takara-machi, Kanazawa, Ishikawa 920-8640, Japan. E-mail ytakuwa{at}med.kanazawa-u.ac.jp
Ca2+ sensitization of vascular smooth muscle (VSM) contraction involves Rho-dependent and Rho-kinase–dependent suppression of myosin phosphatase activity. We previously demonstrated that excitatory agonists in fact induce activation of RhoA in VSM. In this study, we demonstrate a novel Ca2+-dependent mechanism for activating RhoA in rabbit aortic VSM. High KCl-induced membrane depolarization as well as noradrenalin stimulation induced similar extents of sustained contraction in rabbit VSM. Both stimuli also induced similar extents of time-dependent, sustained increases in the amount of an active GTP-bound form of RhoA. Consistent with this, the Rho kinase inhibitors HA1077 and Y27632 inhibited both contraction and the 20-kDa myosin light chain phosphorylation induced by KCl as well as noradrenalin, with similar dose-response relations. Either removal of extracellular Ca2+ or the addition of a dihydropyridine Ca2+ channel antagonist totally abolished KCl-induced Rho stimulation and contraction. The calmodulin inhibitor W7 suppressed KCl-induced Rho activation and contraction. Ionomycin mimicked W7-sensitive Rho activation. The expression of dominant-negative N19RhoA suppressed Ca2+-induced Thr695 phosphorylation of the 110-kDa regulatory subunit of myosin phosphatase and phosphorylation of myosin light chain in VSM cells. Finally, either the combination of extracellular Ca2+ removal and depletion of the intracellular Ca2+ store or the addition of W7 greatly reduced noradrenalin-induced and the thromboxane A2 analogue–induced Rho stimulation and contraction. Taken together, these results indicate the existence of the thus-far unrecognized Ca2+-dependent Rho stimulation mechanism in VSM. Excitatory receptor agonists are suggested to use this pathway for simulating Rho.
Key Words: contraction • smooth muscle • Rho • Rho kinase • calcium
This article has been cited by other articles:
 |
|
 |
|
  Z. Ying, F. R.C. Giachini, R. C. Tostes, and R. C. Webb PYK2/PDZ-RhoGEF Links Ca2+ Signaling to RhoA Arterioscler Thromb Vasc Biol, October 1, 2009; 29(10): 1657 - 1663. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Khromov, N. Choudhury, A. S. Stevenson, A. V. Somlyo, and M. Eto Phosphorylation-dependent Autoinhibition of Myosin Light Chain Phosphatase Accounts for Ca2+ Sensitization Force of Smooth Muscle Contraction J. Biol. Chem., August 7, 2009; 284(32): 21569 - 21579. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Bai and M. J. Sanderson The contribution of Ca2+ signaling and Ca2+ sensitivity to the regulation of airway smooth muscle contraction is different in rats and mice Am J Physiol Lung Cell Mol Physiol, June 1, 2009; 296(6): L947 - L958. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Raina, J. Zacharia, M. Li, and W. G. Wier Activation by Ca2+/calmodulin of an exogenous myosin light chain kinase in mouse arteries J. Physiol., June 1, 2009; 587(11): 2599 - 2612. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. A. Martinez-Lemus, M. A. Hill, and G. A. Meininger The Plastic Nature of the Vascular Wall: A Continuum of Remodeling Events Contributing to Control of Arteriolar Diameter and Structure Physiology, February 1, 2009; 24(1): 45 - 57. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. H. Ratz and A. S. Miner Role of Protein Kinase C{zeta} and Calcium Entry in KCl-Induced Vascular Smooth Muscle Calcium Sensitization and Feedback Control of Cellular Calcium Levels J. Pharmacol. Exp. Ther., February 1, 2009; 328(2): 399 - 408. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Ordonez-Moran, M. J. Larriba, H. G. Palmer, R. A. Valero, A. Barbachano, M. Dunach, A. G. de Herreros, C. Villalobos, M. T. Berciano, M. Lafarga, et al. RhoA-ROCK and p38MAPK-MSK1 mediate vitamin D effects on gene expression, phenotype, and Wnt pathway in colon cancer cells J. Cell Biol., November 17, 2008; 183(4): 697 - 710. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. M. Seok, I. Baek, Y.-H. Kim, Y.-S. Jeong, I.-J. Lee, D. H. Shin, Y. H. Hwang, and I. K. Kim Isoflavone Attenuates Vascular Contraction through Inhibition of the RhoA/Rho-Kinase Signaling Pathway J. Pharmacol. Exp. Ther., September 1, 2008; 326(3): 991 - 998. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. D. Tang and Y. Anfinogenova Physiologic Properties and Regulation of the Actin Cytoskeleton in Vascular Smooth Muscle Journal of Cardiovascular Pharmacology and Therapeutics, June 1, 2008; 13(2): 130 - 140. [Abstract] [PDF]
|
|
|
|
 |
|
 N. Villalba, E. Stankevicius, U. Simonsen, and D. Prieto Rho kinase is involved in Ca2+ entry of rat penile small arteries Am J Physiol Heart Circ Physiol, April 1, 2008; 294(4): H1923 - H1932. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Nordquist, E. Y. Lai, M. Sjoquist, A. Patzak, and A. E. G. Persson Proinsulin C-peptide constricts glomerular afferent arterioles in diabetic mice. A potential renoprotective mechanism Am J Physiol Regulatory Integrative Comp Physiol, March 1, 2008; 294(3): R836 - R841. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Ihara, L. Moffat, J. Ostrander, M. P. Walsh, and J. A. MacDonald Characterization of protein kinase pathways responsible for Ca2+ sensitization in rat ileal longitudinal smooth muscle Am J Physiol Gastrointest Liver Physiol, October 1, 2007; 293(4): G699 - G710. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Nakamura, Y. Koga, H. Sakai, K. Homma, and M. Ikebe cGMP-Dependent Relaxation of Smooth Muscle Is Coupled With the Change in the Phosphorylation of Myosin Phosphatase Circ. Res., September 28, 2007; 101(7): 712 - 722. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. W. Nuno, V. P. Korovkina, S. K. England, and K. G. Lamping RhoA Activation Contributes to Sex Differences in Vascular Contractions Arterioscler Thromb Vasc Biol, September 1, 2007; 27(9): 1934 - 1940. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Osada, Y. Yatomi, T. Ohmori, S. Aoki, S. Hosogaya, and Y. Ozaki Involvement of Sphingosine 1-Phosphate, a Platelet-Derived Bioactive Lipid, in Contraction of Mesangium Cells J. Biochem., September 1, 2007; 142(3): 351 - 355. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. L. Wardle, M. Gu, Y. Ishida, and R. J. Paul Rho kinase is an effector underlying Ca2+-desensitizing hypoxic relaxation in porcine coronary artery Am J Physiol Heart Circ Physiol, July 1, 2007; 293(1): H23 - H29. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Bussemaker, F. Pistrosch, S. Forster, K. Herbrig, P. Gross, J. Passauer, and R. P. Brandes Rho kinase contributes to basal vascular tone in humans: role of endothelium-derived nitric oxide Am J Physiol Heart Circ Physiol, July 1, 2007; 293(1): H541 - H547. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Yoshioka, N. Sugimoto, N. Takuwa, and Y. Takuwa Essential Role for Class II Phosphoinositide 3-kinase {alpha}-Isoform in Ca2+-Induced, Rho- and Rho Kinase-Dependent Regulation of Myosin Phosphatase and Contraction in Isolated Vascular Smooth Muscle Cells Mol. Pharmacol., March 1, 2007; 71(3): 912 - 920. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. A. Azam, K. Yoshioka, S. Ohkura, N. Takuwa, N. Sugimoto, K. Sato, and Y. Takuwa Ca2+-Independent, Inhibitory Effects of Cyclic Adenosine 5'-Monophosphate on Ca2+ Regulation of Phosphoinositide 3-Kinase C2{alpha}, Rho, and Myosin Phosphatase in Vascular Smooth Muscle J. Pharmacol. Exp. Ther., February 1, 2007; 320(2): 907 - 916. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Hirota, E. Pertens, and L. J. Janssen The reverse mode of the Na+/Ca2+ exchanger provides a source of Ca2+ for store refilling following agonist-induced Ca2+ mobilization Am J Physiol Lung Cell Mol Physiol, February 1, 2007; 292(2): L438 - L447. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. J. Dimopoulos, S. Semba, K. Kitazawa, M. Eto, and T. Kitazawa Ca2+-Dependent Rapid Ca2+ Sensitization of Contraction in Arterial Smooth Muscle Circ. Res., January 5, 2007; 100(1): 121 - 129. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. Ito, Y. P. R. Jarajapu, M. B Grant, and H. J Knot Characteristics of myogenic tone in the rat ophthalmic artery Am J Physiol Heart Circ Physiol, January 1, 2007; 292(1): H360 - H368. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Hasegawa, J. Nishimura, N. Niiro, K. Hirano, T. Ishibashi, and H. Kanaide Prostaglandin F2{alpha}, but Not Latanoprost, Increases the Ca2+ Sensitivity of the Pig Iris Sphincter Muscle Invest. Ophthalmol. Vis. Sci., November 1, 2006; 47(11): 4865 - 4871. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. P. T. Ward On Ca2+ sensitivity and the airways: not just any smooth muscle Eur. Respir. J., October 1, 2006; 28(4): 680 - 682. [Full Text] [PDF]
|
|
|
|
|
|
Y. Bai and M. J. Sanderson Modulation of the Ca2+ sensitivity of airway smooth muscle cells in murine lung slices Am J Physiol Lung Cell Mol Physiol, August 1, 2006; 291(2): L208 - L221. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Porter, M. C. Evans, A. S. Miner, K. M. Berg, K. R. Ward, and P. H. Ratz Convergence of Ca2+-desensitizing mechanisms activated by forskolin and phenylephrine pretreatment, but not 8-bromo-cGMP Am J Physiol Cell Physiol, June 1, 2006; 290(6): C1552 - C1559. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. T. Lubomirov, K. Reimann, D. Metzler, V. Hasse, R. Stehle, M. Ito, D. J. Hartshorne, H. Gagov, G. Pfitzer, and R. Schubert Urocortin-Induced Decrease in Ca2+ Sensitivity of Contraction in Mouse Tail Arteries Is Attributable to cAMP-Dependent Dephosphorylation of MYPT1 and Activation of Myosin Light Chain Phosphatase Circ. Res., May 12, 2006; 98(9): 1159 - 1167. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. P. Woodsome, A. Polzin, K. Kitazawa, M. Eto, and T. Kitazawa Agonist- and depolarization-induced signals for myosin light chain phosphorylation and force generation of cultured vascular smooth muscle cells J. Cell Sci., May 1, 2006; 119(9): 1769 - 1780. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. L. Wardle, M. Gu, Y. Ishida, and R. J. Paul Ca2+-desensitizing hypoxic vasorelaxation: pivotal role for the myosin binding subunit of myosin phosphatase (MYPT1) in porcine coronary artery J. Physiol., April 1, 2006; 572(1): 259 - 267. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Thakali, L. Davenport, G. D. Fink, and S. W. Watts Pleiotropic Effects of Hydrogen Peroxide in Arteries and Veins From Normotensive and Hypertensive Rats Hypertension, March 1, 2006; 47(3): 482 - 487. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. L. Losapio, R. S. Sprague, A. J. Lonigro, and A. H. Stephenson 5,6-EET-induced contraction of intralobar pulmonary arteries depends on the activation of Rho-kinase J Appl Physiol, October 1, 2005; 99(4): 1391 - 1396. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Nakakuki, M. Ito, H. Iwasaki, Y. Kureishi, R. Okamoto, N. Moriki, M. Kongo, S. Kato, N. Yamada, N. Isaka, et al. Rho/Rho-Kinase Pathway Contributes to C-Reactive Protein-Induced Plasminogen Activator Inhibitor-1 Expression in Endothelial Cells Arterioscler Thromb Vasc Biol, October 1, 2005; 25(10): 2088 - 2093. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Liu, J. Zuo, E. Pertens, P. B. Helli, and L. J. Janssen Regulation of Rho/ROCK signaling in airway smooth muscle by membrane potential and [Ca2+]i Am J Physiol Lung Cell Mol Physiol, October 1, 2005; 289(4): L574 - L582. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Ohtsu, M. Mifune, G. D. Frank, S. Saito, T. Inagami, S. Kim-Mitsuyama, Y. Takuwa, T. Sasaki, J. D. Rothstein, H. Suzuki, et al. Signal-Crosstalk Between Rho/ROCK and c-Jun NH2-Terminal Kinase Mediates Migration of Vascular Smooth Muscle Cells Stimulated by Angiotensin II Arterioscler Thromb Vasc Biol, September 1, 2005; 25(9): 1831 - 1836. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Szaszi, G. Sirokmany, C. D. Ciano-Oliveira, O. D. Rotstein, and A. Kapus Depolarization induces Rho-Rho kinase-mediated myosin light chain phosphorylation in kidney tubular cells Am J Physiol Cell Physiol, September 1, 2005; 289(3): C673 - C685. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Watanabe, F. M. Faraci, and D. D. Heistad Activation of Rho-associated kinase during augmented contraction of the basilar artery to serotonin after subarachnoid hemorrhage Am J Physiol Heart Circ Physiol, June 1, 2005; 288(6): H2653 - H2658. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Bi, J. Nishimura, N. Niiro, K. Hirano, and H. Kanaide Contractile Properties of the Cultured Vascular Smooth Muscle Cells: The Crucial Role Played by RhoA in the Regulation of Contractility Circ. Res., April 29, 2005; 96(8): 890 - 897. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. H. Ratz, K. M. Berg, N. H. Urban, and A. S. Miner Regulation of smooth muscle calcium sensitivity: KCl as a calcium-sensitizing stimulus Am J Physiol Cell Physiol, April 1, 2005; 288(4): C769 - C783. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Cogolludo, L. Moreno, F. Lodi, J. Tamargo, and F. Perez-Vizcaino Postnatal maturational shift from PKC{zeta} and voltage-gated K+ channels to RhoA/Rho kinase in pulmonary vasoconstriction Cardiovasc Res, April 1, 2005; 66(1): 84 - 93. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Erdos, J. A. Snipes, B. Kis, A. W. Miller, and D. W. Busija Vasoconstrictor mechanisms in the cerebral circulation are unaffected by insulin resistance Am J Physiol Regulatory Integrative Comp Physiol, December 1, 2004; 287(6): R1456 - R1461. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S Shabir, L Borisova, S. Wray, and T Burdyga Rho-kinase inhibition and electromechanical coupling in rat and guinea-pig ureter smooth muscle: Ca2+-dependent and -independent mechanisms J. Physiol., November 1, 2004; 560(3): 839 - 855. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. T. Sylvester The tone of pulmonary smooth muscle: ROK and Rho music? Am J Physiol Lung Cell Mol Physiol, October 1, 2004; 287(4): L624 - L630. [Full Text] [PDF]
|
|
|
|
|
|
L. J. Janssen, T. Tazzeo, J. Zuo, E. Pertens, and S. Keshavjee KCl evokes contraction of airway smooth muscle via activation of RhoA and Rho-kinase Am J Physiol Lung Cell Mol Physiol, October 1, 2004; 287(4): L852 - L858. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B.R. Wamhoff, D.K. Bowles, O.G. McDonald, S. Sinha, A.P. Somlyo, A.V. Somlyo, and G.K. Owens L-type Voltage-Gated Ca2+ Channels Modulate Expression of Smooth Muscle Differentiation Marker Genes via a Rho Kinase/Myocardin/SRF-Dependent Mechanism Circ. Res., August 20, 2004; 95(4): 406 - 414. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. L. Heaps, J. L. Parker, M. Sturek, and D. K. Bowles Altered calcium sensitivity contributes to enhanced contractility of collateral-dependent coronary arteries J Appl Physiol, July 1, 2004; 97(1): 310 - 316. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Kitazawa, A. N. Polzin, and M. Eto CPI-17-deficient smooth muscle of chicken J. Physiol., June 1, 2004; 557(2): 515 - 528. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Ohama, M. Hori, K. Sato, H. Ozaki, and H. Karaki Chronic Treatment with Interleukin-1{beta} Attenuates Contractions by Decreasing the Activities of CPI-17 and MYPT-1 in Intestinal Smooth Muscle J. Biol. Chem., December 5, 2003; 278(49): 48794 - 48804. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. V. Brozovich Rho Signaling: Agonist Stimulation and Depolarization Come Together Circ. Res., September 19, 2003; 93(6): 481 - 483. [Full Text] [PDF]
|
|