Influence of mitochondrial inhibition on global and local [Ca(2+)](I) in rat tail artery.
(2002) In Circulation Research 90(7). p.792-799- Abstract
- Inhibition of oxidative metabolism is often found to decrease contractility of systemic vascular smooth muscle, but not to reduce global [Ca(2+)](i). In the present study, we probe the hypothesis that it is associated with an altered pattern of intracellular Ca(2+) oscillations (waves) influencing force development. In the rat tail artery, mitochondrial inhibitors (rotenone, antimycin A, and cyanide) reduced alpha(1)-adrenoceptor-stimulated force by 50% to 80%, but did not reduce global [Ca(2+)](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... (More)
- Inhibition of oxidative metabolism is often found to decrease contractility of systemic vascular smooth muscle, but not to reduce global [Ca(2+)](i). In the present study, we probe the hypothesis that it is associated with an altered pattern of intracellular Ca(2+) oscillations (waves) influencing force development. In the rat tail artery, mitochondrial inhibitors (rotenone, antimycin A, and cyanide) reduced alpha(1)-adrenoceptor-stimulated force by 50% to 80%, but did not reduce global [Ca(2+)](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 Ca(2+) waves elicited by alpha(1) stimulation. The altered wave pattern, in association with increased basal [Ca(2+)](i), accounted for the unchanged global [Ca(2+)](i). Inhibition of glycolytic ATP production by arsenate caused similar effects on Ca(2+) waves and global [Ca(2+)](i), developing gradually in parallel with decreased contractility. Inhibition of wave activity by the InsP(3) 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 [Ca(2+)](i), suggesting that contraction may at least partly depend on Ca(2+) wave activity. This study therefore indicates that mitochondrial inhibition influences Ca(2+) wave activity, possibly due to a close spatial relationship of mitochondria and the sarcoplasmic reticulum and that this contributes to metabolic vascular relaxation. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/107752
- author
- Swärd, Karl LU ; Dreja, Karl LU ; Lindqvist, Anders LU ; Persson, Erik and Hellstrand, Per LU
- organization
- publishing date
- 2002
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Calcium Signaling : drug effects, Calcium : metabolism, Cyanides : pharmacology, Calcium Signaling : physiology, Enzyme Inhibitors : pharmacology, Female, Intracellular Fluid : metabolism, In Vitro, Glycolysis : drug effects, Isometric Contraction : drug effects, Mitochondria : drug effects, Mitochondria : metabolism, Myosin Light Chains : metabolism, Phosphorylation : drug effects, Rats, Sprague-Dawley, Receptors, alpha-1 : metabolism, Adrenergic, Rotenone : pharmacology, Support, Tail : blood supply, Non-U.S. Gov't, Vasoconstriction : drug effects, Arteries : metabolism, Arteries : drug effects, Arsenates : pharmacology, Antimycin A : pharmacology, Macrolide : pharmacology, Antibiotics, Animal, Adrenergic alpha-Agonists : pharmacology, Uncoupling Agents : pharmacology
- in
- Circulation Research
- volume
- 90
- issue
- 7
- pages
- 792 - 799
- publisher
- American Heart Association
- external identifiers
-
- pmid:11964372
- wos:000175179100009
- scopus:0037134406
- ISSN
- 0009-7330
- DOI
- 10.1161/01.RES.0000015214.40360.84
- language
- English
- LU publication?
- yes
- id
- 7a5aea49-ef43-410f-a36e-2c599ea587b9 (old id 107752)
- date added to LUP
- 2016-04-01 16:48:06
- date last changed
- 2022-03-22 21:08:35
@article{7a5aea49-ef43-410f-a36e-2c599ea587b9,
abstract = {{Inhibition of oxidative metabolism is often found to decrease contractility of systemic vascular smooth muscle, but not to reduce global [Ca(2+)](i). In the present study, we probe the hypothesis that it is associated with an altered pattern of intracellular Ca(2+) oscillations (waves) influencing force development. In the rat tail artery, mitochondrial inhibitors (rotenone, antimycin A, and cyanide) reduced alpha(1)-adrenoceptor-stimulated force by 50% to 80%, but did not reduce global [Ca(2+)](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 Ca(2+) waves elicited by alpha(1) stimulation. The altered wave pattern, in association with increased basal [Ca(2+)](i), accounted for the unchanged global [Ca(2+)](i). Inhibition of glycolytic ATP production by arsenate caused similar effects on Ca(2+) waves and global [Ca(2+)](i), developing gradually in parallel with decreased contractility. Inhibition of wave activity by the InsP(3) 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 [Ca(2+)](i), suggesting that contraction may at least partly depend on Ca(2+) wave activity. This study therefore indicates that mitochondrial inhibition influences Ca(2+) wave activity, possibly due to a close spatial relationship of mitochondria and the sarcoplasmic reticulum and that this contributes to metabolic vascular relaxation.}},
author = {{Swärd, Karl and Dreja, Karl and Lindqvist, Anders and Persson, Erik and Hellstrand, Per}},
issn = {{0009-7330}},
keywords = {{Calcium Signaling : drug effects; Calcium : metabolism; Cyanides : pharmacology; Calcium Signaling : physiology; Enzyme Inhibitors : pharmacology; Female; Intracellular Fluid : metabolism; In Vitro; Glycolysis : drug effects; Isometric Contraction : drug effects; Mitochondria : drug effects; Mitochondria : metabolism; Myosin Light Chains : metabolism; Phosphorylation : drug effects; Rats; Sprague-Dawley; Receptors; alpha-1 : metabolism; Adrenergic; Rotenone : pharmacology; Support; Tail : blood supply; Non-U.S. Gov't; Vasoconstriction : drug effects; Arteries : metabolism; Arteries : drug effects; Arsenates : pharmacology; Antimycin A : pharmacology; Macrolide : pharmacology; Antibiotics; Animal; Adrenergic alpha-Agonists : pharmacology; Uncoupling Agents : pharmacology}},
language = {{eng}},
number = {{7}},
pages = {{792--799}},
publisher = {{American Heart Association}},
series = {{Circulation Research}},
title = {{Influence of mitochondrial inhibition on global and local [Ca(2+)](I) in rat tail artery.}},
url = {{http://dx.doi.org/10.1161/01.RES.0000015214.40360.84}},
doi = {{10.1161/01.RES.0000015214.40360.84}},
volume = {{90}},
year = {{2002}},
}