This Article Full Text Full Text (PDF) Data Supplement All Versions of this Article: 90/7/792    most recent 01.RES.0000015214.40360.84v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Swärd, K. Articles by Hellstrand, P. Search for Related Content PubMed PubMed Citation Articles by Swärd, K. Articles by Hellstrand, P. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Hazardous Substances DB ANTIMYCIN A ARSENIC ACID ARSENIC COMPOUNDS CALCIUM COMPOUNDS CALCIUM, ELEMENTAL ROTENONE Related Collections Calcium cycling/excitation-contraction coupling Cell signalling/signal transduction Imaging Ischemic biology - basic studies Other Vascular biology

(Circulation Research. 2002;90:792.)
© 2002 American Heart Association, Inc.

Cellular Biology

Influence of Mitochondrial Inhibition on Global and Local [Ca²⁺]_i in Rat Tail Artery

Karl Swärd, Karl Dreja, Anders Lindqvist, Erik Persson, Per Hellstrand

From the Department of Physiological Sciences, Lund University, Lund, Sweden.

Correspondence to Karl Swärd, PhD, Dept of Physiological Sciences, Lund University, BMC F12, S-221 84 Lund, Sweden. 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:

				D. Poburko, C.-H. Liao, C. van Breemen, and N. Demaurex Mitochondrial Regulation of Sarcoplasmic Reticulum Ca2+ Content in Vascular Smooth Muscle Cells Circ. Res., January 2, 2009; 104(1): 104 - 112. [Abstract] [Full Text] [PDF]

				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]