Advanced

Increased potassium conductance of brain mitochondria induces resistance to permeability transition by enhancing matrix volume.

Hansson, Magnus LU ; Morota, Saori LU ; Teilum, Maria LU ; Mattiasson, Gustav LU ; Uchino, Hiroyuki and Elmer, Eskil LU (2010) In Journal of Biological Chemistry 285. p.741-750
Abstract
Modulation of K+ conductance of the inner mitochondrial membrane has been proposed to mediate preconditioning in ischemia-reperfusion injury. The mechanism is not entirely understood but it has been linked to a decreased activation of mitochondrial permeability transition (mPT). In the present study, K+ channel activity was mimicked by picomolar concentrations of valinomycin. Isolated brain mitochondria were exposed to continuous infusions of calcium. Monitoring of extramitochondrial Ca2+ and mitochondrial respiration provided a quantitative assay for mPT-sensitivity by determining calcium retention capacity (CRC). Valinomycin and cyclophilin D-inhibition separately and additively increased CRC. Comparable degrees of respiratory uncoupling... (More)
Modulation of K+ conductance of the inner mitochondrial membrane has been proposed to mediate preconditioning in ischemia-reperfusion injury. The mechanism is not entirely understood but it has been linked to a decreased activation of mitochondrial permeability transition (mPT). In the present study, K+ channel activity was mimicked by picomolar concentrations of valinomycin. Isolated brain mitochondria were exposed to continuous infusions of calcium. Monitoring of extramitochondrial Ca2+ and mitochondrial respiration provided a quantitative assay for mPT-sensitivity by determining calcium retention capacity (CRC). Valinomycin and cyclophilin D-inhibition separately and additively increased CRC. Comparable degrees of respiratory uncoupling induced by increased K+ or H+ conductance had opposite effects on mPT sensitivity. Protonophores dose-dependently decreased CRC, demonstrating that so-called mild uncoupling was not beneficial per se. The putative mitoKATP channel opener diazoxide did not mimic the effect of valinomycin. An alkaline matrix pH was required in order for mitochondria to retain calcium, but increased K+ conductance did not result in augmented DeltapH. The beneficial effect of valinomycin on CRC was not mediated by H2O2-induced PKCepsilon activation. In contrast, increased K+ conductance reduced H2O2 generation during calcium infusion. Lowering the osmolarity of the buffer induced an increase in mitochondrial volume and improved CRC similar to valinomycin without inducing uncoupling or otherwise affecting respiration. We propose that increased potassium conductance in brain mitochondria may cause a direct physiological effect on matrix volume inducing resistance to pathological calcium challenges. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Biological Chemistry
volume
285
pages
741 - 750
publisher
ASBMB
external identifiers
  • wos:000273070100075
  • pmid:19880514
  • scopus:73649092745
ISSN
1083-351X
DOI
10.1074/jbc.M109.017731
language
English
LU publication?
yes
id
f36654e7-a510-45ad-850c-39be737b2fc2 (old id 1512372)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/19880514?dopt=Abstract
date added to LUP
2009-12-01 07:59:57
date last changed
2018-05-29 10:32:07
@article{f36654e7-a510-45ad-850c-39be737b2fc2,
  abstract     = {Modulation of K+ conductance of the inner mitochondrial membrane has been proposed to mediate preconditioning in ischemia-reperfusion injury. The mechanism is not entirely understood but it has been linked to a decreased activation of mitochondrial permeability transition (mPT). In the present study, K+ channel activity was mimicked by picomolar concentrations of valinomycin. Isolated brain mitochondria were exposed to continuous infusions of calcium. Monitoring of extramitochondrial Ca2+ and mitochondrial respiration provided a quantitative assay for mPT-sensitivity by determining calcium retention capacity (CRC). Valinomycin and cyclophilin D-inhibition separately and additively increased CRC. Comparable degrees of respiratory uncoupling induced by increased K+ or H+ conductance had opposite effects on mPT sensitivity. Protonophores dose-dependently decreased CRC, demonstrating that so-called mild uncoupling was not beneficial per se. The putative mitoKATP channel opener diazoxide did not mimic the effect of valinomycin. An alkaline matrix pH was required in order for mitochondria to retain calcium, but increased K+ conductance did not result in augmented DeltapH. The beneficial effect of valinomycin on CRC was not mediated by H2O2-induced PKCepsilon activation. In contrast, increased K+ conductance reduced H2O2 generation during calcium infusion. Lowering the osmolarity of the buffer induced an increase in mitochondrial volume and improved CRC similar to valinomycin without inducing uncoupling or otherwise affecting respiration. We propose that increased potassium conductance in brain mitochondria may cause a direct physiological effect on matrix volume inducing resistance to pathological calcium challenges.},
  author       = {Hansson, Magnus and Morota, Saori and Teilum, Maria and Mattiasson, Gustav and Uchino, Hiroyuki and Elmer, Eskil},
  issn         = {1083-351X},
  language     = {eng},
  pages        = {741--750},
  publisher    = {ASBMB},
  series       = {Journal of Biological Chemistry},
  title        = {Increased potassium conductance of brain mitochondria induces resistance to permeability transition by enhancing matrix volume.},
  url          = {http://dx.doi.org/10.1074/jbc.M109.017731},
  volume       = {285},
  year         = {2010},
}