Ischemic Preconditioning Protects Against Gap Junctional Uncoupling in Cardiac Myofibroblasts

Sundset, Rune; Cooper, Marie; Mikalsen, Svein‐Ole; Ytrehus, Kirsti

doi:10.1080/15419060490951772

Cited by 8 publications

(10 citation statements)

References 60 publications

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“…Of special interest is that the suggested major protein kinase C phosphorylation site is S368, positioned in the middle of the repetitive sequence. Protein kinase C is involved in ischemic preconditioning effect in the heart [33], and previous results have shown that preconditioning delays the dephosphorylation in cardiac myocytes in culture [3]. Thus, dephosphorylation may occur because the balance of activity between phosphatases and protein kinase C has been displaced in favour of the phosphatases.…”

Section: Discussionmentioning

confidence: 99%

“…The loss of high-energy phosphate compounds leads to failure of membrane-based ion pumps resulting in increase in extracellular potassium [2]. We have previously shown that neonatal cardiac fibroblasts suffer time-dependent viability loss as a consequence of ischemia-like culture conditions [3]. These cells also respond to cardioprotective strategies in the same way as cardiomyocytes [3,4].…”

Section: Introductionmentioning

confidence: 99%

“…Rat neonatal fibroblasts were isolated from the hearts of 1-2 day old pups by enzymatic dissociating as previous described [3,17]. Mass cultures were grown in Dulbecco's Modified Eagle's Medium supplemented with glutamine and 10% fetal calf serum (Invitrogen) in a humid 5% CO 2 atmosphere at 37 C. Cells were maintained in culture until confluent.…”

Section: Cell Cultures and Incubation In Modified Hepes Buffermentioning

confidence: 99%

“…We have previously shown that neonatal cardiac fibroblasts suffer time-dependent viability loss as a consequence of ischemia-like culture conditions [3]. These cells also respond to cardioprotective strategies in the same way as cardiomyocytes [3,4].…”

Section: Introductionmentioning

confidence: 99%

“…Whereas metabolic inhibition opens Cx43 hemichannels [5], ischemia induces closure of gap junction channels, both when determined electrophysiologically [6] or by transfer of gap junction-permeable dyes [3,7]. Increased cytosolic Ca 2+ concentration, reduced ATP concentration, changes in phosphorylation of Cx43, and acidification, all occurring during ischemia, close gap junction channels [8], whereas a decrease in extracellular Ca 2+ concentration or changes in phosphorylation have been described to open Cx43 hemichannels [1].…”

Section: Introductionmentioning

confidence: 99%

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Ischemia Induces Closure of Gap Junctional Channels and Opening of Hemichannels in Heart-derived Cells and Tissue

Johansen

Cruciani

Sundset

et al. 2011

Cell Physiol Biochem

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Aim: Gap junction intercellular communication (GJIC) and hemichannel permeability may have important roles during an ischemic insult. Our aim was to evaluate the effect of ischemia on gap junction channels and hemichannels. Methods: We used neonatal rat heart myofibroblasts and simulated ischemia with a HEPES buffer with high potassium, low pH, absence of glucose, and oxygen tension was reduced by dithionite. Microinjection, western blot, immunofluorescence, cell viability and dye uptake were used to evaluate the effects induced by dithionite. Isolated perfused rat hearts were used to analyse infarct size. Results: Short period with simulated ischemia reduced the ability to transfer a dye between neighbouring cells, which indicated reduced GJIC. Prolonged exposure to simulated ischemia caused opening of hemichannels, and cell death was apparent while gap junction channels remained closed. Connexin 43 became partially dephosphorylated and the total amount decreased during simulated ischemia. We were not able to detect the alternative hemichannel-forming protein, Pannexin 1, in these cells. The potential importance of Connexin 43 or Pannexin 1 hemichannels in ischemia-induced infarct in the intact heart was studied by perfusion of the heart in the presence of peptides that block one or the other type of hemichannels. The connexin-derived peptide, Gap26, significantly reduced the infract/risk zone ratio (control 48.7±4.2% and Gap26 19.4±4.1%, p<0.001), while the pannexin-derived peptide, ¹⁰Panx1, did not change infarct/risk ratio. Conclusion: Connexin 43 is most likely responsible for both closure of gap junction channels and opening of hemichannels during simulated ischemia in neonatal rat heart myofibroblasts. Opening of connexin 43 hemichannels during ischemia-reperfusion seems to be an important mechanism for ischemia-reperfusion injury in the heart. By preventing the opening of these channels during early ischemia-reperfusion the infarct size becomes significantly reduced.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Cell Cultures and Incubation In Modified Hepes Buffermentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Ischemia Induces Closure of Gap Junctional Channels and Opening of Hemichannels in Heart-derived Cells and Tissue

Johansen

Cruciani

Sundset

et al. 2011

Cell Physiol Biochem

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The Multi-Domain Fibroblast/Myocyte Coupling in the Cardiac Tissue: A Theoretical Study

Greisas

Zlochiver

2016

Cardiovasc Eng Tech

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Cardiac fibroblast proliferation and concomitant collagenous matrix accumulation (fibrosis) develop during multiple cardiac pathologies. Recent studies have demonstrated direct electrical coupling between myocytes and fibroblasts in vitro, and assessed the electrophysiological implications of such coupling. However, in the living tissues, such coupling has not been demonstrated, and only indirect coupling via the extracellular space is likely to exist. In this study we employed a multi-domain model to assess the modulation of the cardiac electrophysiological properties by neighboring fibroblasts assuming only indirect coupling. Numerical simulations in 1D and 2D human atrial models showed that extracellular coupling sustains a significant impact on conduction velocity (CV) and a less significant effect on the action potential duration. Both CV and the slope of the CV restitution increased with increasing fibroblast density. This effect was more substantial for lower extracellular conductance. In 2D, spiral waves exhibited reduced frequency with increasing fibroblast density, and the propensity of wavebreaks and complex dynamics at high pacing rates significantly increased.

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Connexin, connection, conductance: Towards understanding induction of arrhythmias?

2009

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Ischemic Preconditioning Protects Against Gap Junctional Uncoupling in Cardiac Myofibroblasts

Cited by 8 publications

References 60 publications

Ischemia Induces Closure of Gap Junctional Channels and Opening of Hemichannels in Heart-derived Cells and Tissue

Ischemia Induces Closure of Gap Junctional Channels and Opening of Hemichannels in Heart-derived Cells and Tissue

The Multi-Domain Fibroblast/Myocyte Coupling in the Cardiac Tissue: A Theoretical Study

Connexin, connection, conductance: Towards understanding induction of arrhythmias?

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