Published online before print March 14, 2002, doi: 10.1161/01.RES.0000015214.40360.84
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Submitted on July 2, 2001
Revised on February 28, 2002
Accepted on March 1, 2002
Influence of Mitochondrial Inhibition on Global and Local [Ca2+]i in Rat Tail Artery
Karl Swärd *;
From the Department of Physiological Sciences, Lund University, Lund, Sweden.
* To whom correspondence should be addressed. E-mail: karl.sward{at}mphy.lu.se.
Inhibition of oxidative metabolism is often found to decrease contractility of systemic vascular smooth muscle, but not to reduce global [Ca2+]i. In the present study, we probe the hypothesis that it is associated with an altered pattern of intracellular Ca2+ oscillations (waves) influencing force development. In the rat tail artery, mitochondrial inhibitors (rotenone, antimycin A, and cyanide) reduced 
1-adrenoceptor--stimulated force by 50% to 80%, but did not reduce global [Ca2+]i. Less relaxation (about 30%) was observed after inhibition of myosin phosphatase activity with calyculin A, suggesting that part of the metabolic sensitivity involves the regulation of myosin 20-kDa light chain phosphorylation, although no decrease in phosphorylation was found in freeze-clamped tissue. Confocal imaging revealed that the mitochondrial inhibitors increased the frequency but reduced the amplitude of asynchronous cellular Ca2+ waves elicited by 1 stimulation. The altered wave pattern, in association with increased basal [Ca2+]i, accounted for the unchanged global [Ca2+]i. Inhibition of glycolytic ATP production by arsenate caused similar effects on Ca2+ waves and global [Ca2+]i, developing gradually in parallel with decreased contractility. Inhibition of wave activity by the InsP3 receptor antagonist 2-APB correlated closely with relaxation. Furthermore, abolition of waves with thapsigargin in the presence of verapamil reduced force by about 50%, despite unaltered global [Ca2+]i, suggesting that contraction may at least partly depend on Ca2+ wave activity. This study therefore indicates that mitochondrial inhibition influences Ca2+ wave activity, possibly due to a close spatial relationship of mitochondria and the sarcoplasmic reticulum and that this contributes to metabolic vascular relaxation.
Key words: arterial smooth muscle • metabolic inhibition • myosin phosphorylation • calcium waves • confocal imaging
This article has been cited by other articles:
 |
|
 |
|
  O. B. Balemba, A. C. Bartoo, M. T. Nelson, and G. M. Mawe Role of mitochondria in spontaneous rhythmic activity and intracellular calcium waves in the guinea pig gallbladder smooth muscle Am J Physiol Gastrointest Liver Physiol, February 1, 2008; 294(2): G467 - G476. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Chalmers and J. G. McCarron The mitochondrial membrane potential and Ca2+ oscillations in smooth muscle J. Cell Sci., January 1, 2008; 121(1): 75 - 85. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Albinsson and P. Hellstrand Integration of signal pathways for stretch-dependent growth and differentiation in vascular smooth muscle Am J Physiol Cell Physiol, August 1, 2007; 293(2): C772 - C782. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Q. Xi, S. Y. Cheranov, and J. H. Jaggar Mitochondria-Derived Reactive Oxygen Species Dilate Cerebral Arteries by Activating Ca2+ Sparks Circ. Res., August 19, 2005; 97(4): 354 - 362. [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]
|
|
|
|
 |
|
 J. J. Andresen, F. M. Faraci, and D. D. Heistad Vasomotor responses in MnSOD-deficient mice Am J Physiol Heart Circ Physiol, September 1, 2004; 287(3): H1141 - H1148. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Y. Cheranov and J. H. Jaggar Mitochondrial modulation of Ca2+ sparks and transient KCa currents in smooth muscle cells of rat cerebral arteries J. Physiol., May 1, 2004; 556(3): 755 - 771. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. D. Thorne and R. J. Paul Effects of organ culture on arterial gene expression and hypoxic relaxation: role of the ryanodine receptor Am J Physiol Cell Physiol, April 1, 2003; 284(4): C999 - C1005. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. J. Heppner, A. D. Bonev, L. F. Santana, and M. T. Nelson Alkaline pH shifts Ca2+ sparks to Ca2+ waves in smooth muscle cells of pressurized cerebral arteries Am J Physiol Heart Circ Physiol, December 1, 2002; 283(6): H2169 - H2176. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Dreja, M. Voldstedlund, J. Vinten, J. Tranum-Jensen, P. Hellstrand, and K. Sward Cholesterol Depletion Disrupts Caveolae and Differentially Impairs Agonist-Induced Arterial Contraction Arterioscler. Thromb. Vasc. Biol., August 1, 2002; 22(8): 1267 - 1272. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Lindqvist, K. Dreja, K. Sward, and P. Hellstrand Effects of oxygen tension on energetics of cultured vascular smooth muscle Am J Physiol Heart Circ Physiol, July 1, 2002; 283(1): H110 - H117. [Abstract] [Full Text] [PDF]
|
|