Circulation Research. 2001;88:1283-1290
Published online before print June 7, 2001, doi: 10.1161/hh1201.092035
Published online before print June 7, 2001, doi: 10.1161/hh1201.092035
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
© 2001 American Heart Association, Inc.
Integrative Physiology |
Distinct Pathways of Ca2+ Sensitization in Porcine Coronary Artery
Effects of Rho-Related Kinase and Protein Kinase C Inhibition on Force and Intracellular Ca2+
From the Department of Molecular and Cellular Physiology, University of Cincinnati College of Medicine, Cincinnati, Ohio.
Correspondence to Dr Richard Paul, Department of Molecular and Cellular Physiology, University of Cincinnati College of Medicine, 231 Albert Sabin Way, Cincinnati, OH 45267-0576. E-mail richard.paul{at}uc.edu
Abstract
Abstract—Alterations of the Ca2+ sensitivity of contraction have been reported for porcine coronary artery, but the mechanisms are not clearly understood. We investigated the mechanism(s) of Ca2+ sensitization in response to the thromboxane A2 analogue (U46619). Our hypothesis is that different mechanisms of Ca2+ sensitization could be distinguished by their distinct time courses. Therefore, we measured the time course of [Ca2+]i and isometric force simultaneously in an intact artery after a single addition of U46619. The initial transient phase was associated with Ca2+ release from the sarcoplasmic reticulum, whereas the maintained phase was associated with Ca2+ influx. Two distinct types of Ca2+ sensitization characterized these phases with either protein kinase C (PKC)-mediated or Rho-kinase–mediated mechanisms. Their effects were quite distinct on the basis of the time courses over which the sensitization was effective. PKC inhibition (1 µmol/L calphostin C) had a much greater effect in the initial phase, diminishing the size of the transient and prolonging the rise in force and the decline in [Ca2+]i. There were limited effects on the sustained force. Rho-kinase inhibition (10 µmol/L Y27632), in contrast, nearly abolished the sustained force but had a lesser effect on the transient phase. Neither inhibitor had any effect on the force versus [Ca2+]i relations for KCl contractures. Our evidence suggests that both PKC-mediated and Rho-kinase–mediated Ca2+ sensitizations are present in coronary arteries, but the latter is dominant in thromboxane A2 receptor–mediated contraction.
Key Words: coronary arteries • Ca2+ sensitization • protein kinase C • Rho-kinase • U46619
This article has been cited by other articles:
 |
|
 |
|
  K. Maruko, V. M. Stiffel, and R. D. Gilbert The Effect of Long-term Hypoxia on Tension and Intracellular Calcium Responses Following Stimulation of the Thromboxane A2 Receptor in the Left Anterior Descending Coronary Artery of Fetal Sheep Reproductive Sciences, April 1, 2009; 16(4): 364 - 372. [Abstract] [PDF]
|
|
|
|
 |
|
 S. A. Gupte, P. M. Kaminski, S. George, L. Kouznestova, S. C. Olson, R. Mathew, T. H. Hintze, and M. S. Wolin Peroxide generation by p47phox-Src activation of Nox2 has a key role in protein kinase C-induced arterial smooth muscle contraction Am J Physiol Heart Circ Physiol, April 1, 2009; 296(4): H1048 - H1057. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. L. Neppl, L. T. Lubomirov, K. Momotani, G. Pfitzer, M. Eto, and A. V. Somlyo Thromboxane A2-induced Bi-directional Regulation of Cerebral Arterial Tone J. Biol. Chem., March 6, 2009; 284(10): 6348 - 6360. [Abstract] [Full Text] [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]
|
|
|
|
 |
|
 K. Nobe, T. Yamazaki, T. Kumai, M. Okazaki, S. Iwai, T. Hashimoto, S. Kobayashi, K. Oguchi, and K. Honda Alterations of Glucose-Dependent and -Independent Bladder Smooth Muscle Contraction in Spontaneously Hypertensive and Hyperlipidemic Rat J. Pharmacol. Exp. Ther., February 1, 2008; 324(2): 631 - 642. [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. Oka, N. Homma, L. Taraseviciene-Stewart, K. G. Morris, D. Kraskauskas, N. Burns, N. F. Voelkel, and I. F. McMurtry Rho Kinase-Mediated Vasoconstriction Is Important in Severe Occlusive Pulmonary Arterial Hypertension in Rats Circ. Res., March 30, 2007; 100(6): 923 - 929. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Nobe, M. Miyatake, T. Sone, and K. Honda High-Glucose-Altered Endothelial Cell Function Involves Both Disruption of Cell-to-Cell Connection and Enhancement of Force Development J. Pharmacol. Exp. Ther., August 1, 2006; 318(2): 530 - 539. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. P. Smith, R. A. Dombkowski, J. T. Wincko, and K. R. Olson Effect of pH on trout blood vessels and gill vascular resistance J. Exp. Biol., July 1, 2006; 209(13): 2586 - 2594. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Budzyn, M. Paull, P. D. Marley, and C. G. Sobey Segmental Differences in the Roles of Rho-Kinase and Protein Kinase C in Mediating Vasoconstriction J. Pharmacol. Exp. Ther., May 1, 2006; 317(2): 791 - 796. [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]
|
|
|
|
|
|
V. A. Snetkov, G. A Knock, L. Baxter, G. D. Thomas, J. P. T. Ward, and P. I. Aaronson Mechanisms of the prostaglandin F2{alpha}-induced rise in [Ca2+]i in rat intrapulmonary arteries J. Physiol., February 15, 2006; 571(1): 147 - 163. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Weigand, J. T. Sylvester, and L. A. Shimoda Mechanisms of endothelin-1-induced contraction in pulmonary arteries from chronically hypoxic rats Am J Physiol Lung Cell Mol Physiol, February 1, 2006; 290(2): L284 - L290. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Gu, G. D Thorne, R. L Wardle, Y. Ishida, and R. J Paul Ca2+-independent hypoxic vasorelaxation in porcine coronary artery J. Physiol., February 1, 2005; 562(3): 839 - 846. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. KUMAR, R. MURPHY, P. ROBINSON, L. WEI, and A. M. BORIEK Cyclic mechanical strain inhibits skeletal myogenesis through activation of focal adhesion kinase, Rac-1 GTPase, and NF-{kappa}B transcription factor FASEB J, October 1, 2004; 18(13): 1524 - 1535. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Nagaoka, Y. Morio, N. Casanova, N. Bauer, S. Gebb, I. McMurtry, and M. Oka Rho/Rho kinase signaling mediates increased basal pulmonary vascular tone in chronically hypoxic rats Am J Physiol Lung Cell Mol Physiol, October 1, 2004; 287(4): L665 - L672. [Abstract] [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]
|
|
|
|
|
|
C. Martin, R. Goggel, A.-R. Ressmeyer, and S. Uhlig Pressor responses to platelet-activating factor and thromboxane are mediated by Rho-kinase Am J Physiol Lung Cell Mol Physiol, July 1, 2004; 287(1): L250 - L257. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. A. Wehrwein, C. A. Northcott, R. D. Loberg, and S. W. Watts Rho/Rho Kinase and Phosphoinositide 3-Kinase Are Parallel Pathways in the Development of Spontaneous Arterial Tone in Deoxycorticosterone Acetate-Salt Hypertension J. Pharmacol. Exp. Ther., June 1, 2004; 309(3): 1011 - 1019. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. D. Thorne, G. M. Hilliard, and R. J. Paul Vascular oxygen sensing: detection of novel candidates by proteomics and organ culture J Appl Physiol, February 1, 2004; 96(2): 802 - 808. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Kandabashi, H. Shimokawa, K. Miyata, I. Kunihiro, Y. Eto, K. Morishige, Y. Matsumoto, K. Obara, K. Nakayama, S. Takahashi, et al. Evidence for Protein Kinase C-Mediated Activation of Rho- Kinase in a Porcine Model of Coronary Artery Spasm Arterioscler Thromb Vasc Biol, December 1, 2003; 23(12): 2209 - 2214. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. E. DiSanto Corpus Cavernosum Smooth Muscle Physiology: A Role for Sex Hormones? J Androl, November 1, 2003; 24(6_suppl): S6 - S16. [Full Text] [PDF]
|
|
|
|
 |
|
 A. P. SOMLYO and A. V. SOMLYO Ca2+ Sensitivity of Smooth Muscle and Nonmuscle Myosin II: Modulated by G Proteins, Kinases, and Myosin Phosphatase Physiol Rev, October 1, 2003; 83(4): 1325 - 1358. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Ghisdal, G. Vandenberg, and N. Morel Rho-dependent kinase is involved in agonist-activated calcium entry in rat arteries J. Physiol., September 15, 2003; 551(3): 855 - 867. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Wickman, C. Lan, and B. Vollrath Functional Roles of the Rho/Rho Kinase Pathway and Protein Kinase C in the Regulation of Cerebrovascular Constriction Mediated by Hemoglobin: Relevance to Subarachnoid Hemorrhage and Vasospasm Circ. Res., April 18, 2003; 92(7): 809 - 816. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. Randriamboavonjy, R. Busse, and I. Fleming 20-HETE-Induced Contraction of Small Coronary Arteries Depends on the Activation of Rho-Kinase Hypertension, March 1, 2003; 41(3): 801 - 806. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. S. Damron, N. Kanaya, Y. Homma, S.-O. Kim, and P. A. Murray Role of PKC, tyrosine kinases, and Rho kinase in alpha -adrenoreceptor-mediated PASM contraction Am J Physiol Lung Cell Mol Physiol, November 1, 2002; 283(5): L1051 - L1064. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. G. Lamping Enhanced Contractile Mechanisms in Vasospasm: Is Endothelial Dysfunction the Whole Story? Circulation, April 2, 2002; 105(13): 1520 - 1522. [Full Text] [PDF]
|
|
|
|
|
|
H.-M. Shin, H.-D. Je, C. Gallant, T. C. Tao, D. J. Hartshorne, M. Ito, and K. G. Morgan Differential Association and Localization of Myosin Phosphatase Subunits During Agonist-Induced Signal Transduction in Smooth Muscle Circ. Res., March 22, 2002; 90(5): 546 - 553. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Q. J. Li and L. J. Janssen Membrane currents in canine bronchial artery and their regulation by excitatory agonists Am J Physiol Lung Cell Mol Physiol, June 1, 2002; 282(6): L1358 - L1365. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H.-M. Shin, H.-D. Je, C. Gallant, T. C. Tao, D. J. Hartshorne, M. Ito, and K. G. Morgan Differential Association and Localization of Myosin Phosphatase Subunits During Agonist-Induced Signal Transduction in Smooth Muscle Circ. Res., March 22, 2002; 90(5): 546 - 553. [Abstract] [Full Text] [PDF]
|
|