Functional role of connexin43 gap junction channels in adult mouse heart assessed by inducible gene deletion

Eckardt, Dominik

doi:10.1016/j.yjmcc.2003.10.006

Cited by 134 publications

(121 citation statements)

References 36 publications

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“…They develop normally as Cx43 heterozygous animals while the remaining floxed Cx43 allele is excised upon 4-hydroxytamoxifen (tamoxifen) treatment. 29 Tamoxifen treatment was given to both Cx43 Cre-ER(T)/fl and Cx43 fl/fl control animals and was ip injected at a dose of 1 mg in 100 mL sunflower oil and applied for five consecutive days; animals were sacrificed and used for experiments on Day 6 after the end of tamoxifen treatment. Animal weight was in the 27-28 g range.…”

Section: Conditional Cx43 Ko Animal Experimentsmentioning

confidence: 99%

At the cross-point of connexins, calcium, and ATP: blocking hemichannels inhibits vasoconstriction of rat small mesenteric arteries

et al. 2016

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Section: Conditional Cx43 Ko Animal Experimentsmentioning

confidence: 99%

At the cross-point of connexins, calcium, and ATP: blocking hemichannels inhibits vasoconstriction of rat small mesenteric arteries

et al. 2016

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“…As proof of principle, PMN were isolated from tamoxifen-inducible Cx43 conditionally deleted mice (Eckardt et al 2004) and examined for ATP release. These studies revealed that ATP release correlated with the degree of Cx43 expression.…”

Section: Mechanisms Of Pmn-derived Atp Releasementioning

confidence: 99%

Neutrophils as Sources of Extracellular Nucleotides: Functional Consequences at the Vascular Interface

Eltzschig

MacManus

Colgan

2008

Trends in Cardiovascular Medicine

108

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Nucleotide signaling is currently an area of intense investigation. Extracellular ATP liberated during hypoxia or inflammation can either signal directly to purinergic receptors or, following phosphohydrolytic metabolism, can activate surface adenosine (Ado) receptors. Given the association of polymorphonuclear leukocytes (PMN) with adenine nucleotide / nucleoside signaling in the inflammatory milieu, it was recently demonstrated that PMN actively release ATP via a connexin 43 (Cx43) hemichannel-dependent mechanism. Here we review the mechanisms of ATP release and subsequent functional implications of ATP metabolism at the interface between PMN and vascular endothelial cells during inflammation and in hypoxia.

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“…The major ventricular gap junction protein is Cx43, and downregulation of this connexin has been associated with arrhythmic risk [20][21][22]. This protein is regulated by phosphorylation, with the unphosphorylated version of the channel generally showing a reduced open probability that results in reduced gap junction conductance [23].…”

Section: Halon and Epinephrine Reduce Conduction Velocitymentioning

confidence: 99%

“…Genetic downregulation of Cx43 is associated with slow conduction and arrhythmogenic death [22], and several reports have demonstrated an inverse relationship between conduction velocity and non-phosphorylated Cx43 [25,26]. Therefore, it seems plausible thatphosphorylation-dependent changes inCx43 cause the gap junction uncoupling that may underlie part of the phenomenon of cardiac sensitization.…”

Section: The Combination Of Halon and Epinephrine Reduced Conduction mentioning

confidence: 99%

A possible mechanism of halocarbon-induced cardiac sensitization arrhythmias

Jing

Jesús

Iravanian

et al. 2006

Journal of Molecular and Cellular Cardiology

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Cardiac sensitization is the term used for malignant ventricular arrhythmias associated with exposure to inhaled halocarbons in the presence of catecholamines. We investigated the electrophysiological changes associated with cardiomyocyte exposure to epinephrine and a halocarbon known to be associated with cardiac sensitization (halon 1301, CF 3 Br). Cardiomyocytes (CMs) were isolated from neonatal rats and grown on multielectrode arrays (MEAs). Upon exposure to epinephrine, the CM inter-spike interval (ISI) was decreased 14% at 10 µg/L (P<0.05) and 27% at 100 µg/L (P<0.05) as compared to baseline. Halon alone (50 mg/L) mildly prolonged the field potential (FP) duration (7%). CMs exposed to combinations of epinephrine (100 µg/L) and halon (50 mg/L) for 15 min showed a blunted increase in the ISI (35±12%) and a 38% decrease in conduction velocity (P<0.05) when compared to epinephrine alone. There was no change in field potential properties, but dephosphorylated connexin 43 (Cx43) was increased 60±16% with the combination as compared to epinephrine alone (P<0.05). Treatment with okadaic acid, a phosphatase inhibitor, prevented the Cx43 dephosphorylation and the reduction in conduction velocity upon exposure to halon and epinephrine. Moreover, the electrophysiological changes induced by epinephrine and halon were indistinguishable from those seen with the gap junction inhibitor heptanol. In conclusion, the combination of a halocarbon and epinephrine results in a unique electrophysiological signature including slow conduction that may explain, in part, the basis for cardiac sensitization. The slowing of conduction is most likely related to changes in the phosphorylation state of Cx43.

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Functional role of connexin43 gap junction channels in adult mouse heart assessed by inducible gene deletion

Cited by 134 publications

References 36 publications

At the cross-point of connexins, calcium, and ATP: blocking hemichannels inhibits vasoconstriction of rat small mesenteric arteries

At the cross-point of connexins, calcium, and ATP: blocking hemichannels inhibits vasoconstriction of rat small mesenteric arteries

Neutrophils as Sources of Extracellular Nucleotides: Functional Consequences at the Vascular Interface

A possible mechanism of halocarbon-induced cardiac sensitization arrhythmias

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