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Article ; Online: Sympathetic vasoconstriction takes an unexpected pannexin detour.

Nielsen, Morten Schak

2015 Volume 8, Issue 364, Page(s) fs4

Abstract: Sympathetic vasoconstriction plays an important role in the control of blood pressure and the distribution of blood flow. In this issue of Science Signaling, Billaud et al. show that sympathetic vasoconstriction occurs through a complex scheme involving ... ...

Abstract	Sympathetic vasoconstriction plays an important role in the control of blood pressure and the distribution of blood flow. In this issue of Science Signaling, Billaud et al. show that sympathetic vasoconstriction occurs through a complex scheme involving the activation of large-pore pannexin 1 channels and the subsequent release of adenosine triphosphate that promotes contraction in an autocrine and paracrine manner. This elaborate mechanism may function as a point of intercept for other signaling pathways—for example, in relation to the phenomenon "functional sympatholysis," in which exercise abrogates sympathetic vasoconstriction in skeletal muscle. Because pannexin 1 channels are inhibited by nitric oxide, they may function as a switch to turn off adrenergic signaling in skeletal muscle during exercise.
MeSH term(s)	Animals ; Blood Pressure/physiology ; Connexins/metabolism ; Humans ; Muscle, Smooth, Vascular/metabolism ; Nerve Tissue Proteins/metabolism ; Receptors, Adrenergic, alpha-1/metabolism ; Signal Transduction/physiology ; Vasoconstriction/physiology
Chemical Substances	Connexins ; Nerve Tissue Proteins ; Receptors, Adrenergic, alpha-1
Language	English
Publishing date	2015-02-17
Publishing country	United States
Document type	Comment ; Journal Article ; Review
ZDB-ID	2417226-1
ISSN	1937-9145 ; 1945-0877
ISSN (online)	1937-9145
ISSN	1945-0877
DOI	10.1126/scisignal.aaa7312
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Lateralized gap junctions in pulmonary hypertension: lost but not alone.

Nielsen, Morten Schak

Heart rhythm

2012 Volume 9, Issue 7, Page(s) 1141–1142

MeSH term(s)	Animals ; Connexin 43/physiology ; Desmosomes/physiology ; Gap Junctions/physiology ; Hypertension, Pulmonary/physiopathology ; Microtubule-Associated Proteins/physiology
Chemical Substances	Connexin 43 ; Microtubule-Associated Proteins
Language	English
Publishing date	2012-07
Publishing country	United States
Document type	Comment ; Editorial
ZDB-ID	2229357-7
ISSN	1556-3871 ; 1547-5271
ISSN (online)	1556-3871
ISSN	1547-5271
DOI	10.1016/j.hrthm.2012.03.053
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Article ; Online: Myocyte-fibroblast interactions--risky connections.

Nielsen, Morten Schak

Heart rhythm

2009 Volume 6, Issue 11, Page(s) 1650–1651

MeSH term(s)	Arrhythmias, Cardiac/physiopathology ; Cell Communication/physiology ; Fibroblasts/physiology ; Gap Junctions/physiology ; Humans ; Myocytes, Cardiac/physiology
Language	English
Publishing date	2009-11
Publishing country	United States
Document type	Comment ; Editorial
ZDB-ID	2229357-7
ISSN	1556-3871 ; 1547-5271
ISSN (online)	1556-3871
ISSN	1547-5271
DOI	10.1016/j.hrthm.2009.08.025
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Article ; Online: Structural determinants underlying permeant discrimination of the Cx43 hemichannel.

Nielsen, Brian Skriver / Zonta, Francesco / Farkas, Thomas / Litman, Thomas / Nielsen, Morten Schak / MacAulay, Nanna

The Journal of biological chemistry

2019 Volume 294, Issue 45, Page(s) 16789–16803

Abstract: Connexin (Cx) gap junction channels comprise two hemichannels in neighboring cells, and their permeability is well-described, but permeabilities of the single Cx hemichannel remain largely unresolved. Moreover, determination of isoform-specific Cx ... ...

Abstract	Connexin (Cx) gap junction channels comprise two hemichannels in neighboring cells, and their permeability is well-described, but permeabilities of the single Cx hemichannel remain largely unresolved. Moreover, determination of isoform-specific Cx hemichannel permeability is challenging because of concurrent expression of other channels with similar permeability profiles and inhibitor sensitivities. The mammalian Cx hemichannels Cx30 and Cx43 are gated by extracellular divalent cations, removal of which promotes fluorescent dye uptake in both channels but atomic ion conductance only through Cx30. To determine the molecular determinants of this difference, here we employed chimeras and mutagenesis of predicted pore-lining residues in Cx43. We expressed the mutated channels in
MeSH term(s)	Amino Acid Sequence ; Cell Membrane/metabolism ; Connexin 43/chemistry ; Connexin 43/metabolism ; Electrophysiological Phenomena ; Molecular Dynamics Simulation ; Permeability ; Porosity ; Protein Conformation ; Protein Isoforms/chemistry ; Protein Isoforms/metabolism ; Substrate Specificity
Chemical Substances	Connexin 43 ; Protein Isoforms
Language	English
Publishing date	2019-09-25
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2997-x
ISSN	1083-351X ; 0021-9258
ISSN (online)	1083-351X
ISSN	0021-9258
DOI	10.1074/jbc.RA119.007732
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Article ; Online: T-type Ca

Jensen, Lars Jørn / Nielsen, Morten Schak / Salomonsson, Max / Sørensen, Charlotte Mehlin

Channels (Austin, Tex.)

2017 Volume 11, Issue 3, Page(s) 183–195

Abstract: L-type voltage gated ... ...

Abstract	L-type voltage gated Ca
Language	English
Publishing date	2017-05-04
Publishing country	United States
Document type	Journal Article
ISSN	1933-6969
ISSN (online)	1933-6969
DOI	10.1080/19336950.2016.1273997
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Article ; Online: Pannexin 1 activation and inhibition is permeant-selective.

Nielsen, Brian Skriver / Toft-Bertelsen, Trine Lisberg / Lolansen, Sara Diana / Anderson, Connor L / Nielsen, Morten Schak / Thompson, Roger J / MacAulay, Nanna

The Journal of physiology

2020 Volume 598, Issue 2, Page(s) 361–379

Abstract: Key points: The large-pore channel pannexin 1 (Panx1) is expressed in many cell types and can open upon different, yet not fully established, stimuli. Panx1 permeability is often inferred from channel permeability to fluorescent dyes, but it is ... ...

Abstract	Key points: The large-pore channel pannexin 1 (Panx1) is expressed in many cell types and can open upon different, yet not fully established, stimuli. Panx1 permeability is often inferred from channel permeability to fluorescent dyes, but it is currently unknown whether dye permeability translates to permeability to other molecules. Cell shrinkage and C-terminal cleavage led to a Panx1 open-state with increased permeability to atomic ions (current), but did not alter ethidium uptake. Panx1 inhibitors affected Panx1-mediated ion conduction differently from ethidium permeability, and inhibitor efficiency towards a given molecule therefore cannot be extrapolated to its effects on the permeability of another. We conclude that ethidium permeability does not reflect equal permeation of other molecules and thus is no measure of general Panx1 activity. Abstract: Pannexin 1 (Panx1) is a large-pore membrane channel connecting the extracellular milieu with the cell interior. While several activation regimes activate Panx1 in a variety of cell types, the selective permeability of an open Panx1 channel remains unresolved: does a given activation paradigm increase Panx1's permeability towards all permeants equally and does fluorescent dye flux serve as a proxy for biological permeation through an open channel? To explore permeant-selectivity of Panx1 activation and inhibition, we employed Panx1-expressing Xenopus laevis oocytes and HEK293T cells. We report that different mechanisms of activation of Panx1 differentially affected ethidium and atomic ion permeation. Most notably, C-terminal truncation or cell shrinkage elevated Panx1-mediated ion conductance, but had no effect on ethidium permeability. In contrast, extracellular pH changes predominantly affected ethidium permeability but not ionic conductance. High [K
MeSH term(s)	Animals ; Connexins/physiology ; Fluorescent Dyes ; Glutamic Acid ; HEK293 Cells ; Humans ; Ion Channels/physiology ; Lactic Acid ; Nerve Tissue Proteins/physiology ; Oocytes ; Xenopus laevis
Chemical Substances	Connexins ; Fluorescent Dyes ; Ion Channels ; Nerve Tissue Proteins ; PANX1 protein, human ; Lactic Acid (33X04XA5AT) ; Glutamic Acid (3KX376GY7L)
Language	English
Publishing date	2020-01-06
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	3115-x
ISSN	1469-7793 ; 0022-3751
ISSN (online)	1469-7793
ISSN	0022-3751
DOI	10.1113/JP278759
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Article ; Online: Permeant-specific gating of connexin 30 hemichannels.

Nielsen, Brian Skriver / Alstrom, Jette Skov / Nicholson, Bruce J / Nielsen, Morten Schak / MacAulay, Nanna

The Journal of biological chemistry

2017 Volume 292, Issue 49, Page(s) 19999–20009

Abstract: Gap junctions confer interconnectivity of the cytoplasm in neighboring cells via docking of two connexons expressed in each of the adjacent membranes. Undocked connexons, referred to as hemichannels, may open and connect the cytoplasm with the ... ...

Abstract	Gap junctions confer interconnectivity of the cytoplasm in neighboring cells via docking of two connexons expressed in each of the adjacent membranes. Undocked connexons, referred to as hemichannels, may open and connect the cytoplasm with the extracellular fluid. The hemichannel configuration of connexins (Cxs) displays isoform-specific permeability profiles that are not directly determined by the size and charge of the permeant. To further explore Ca
MeSH term(s)	Amino Acid Substitution ; Animals ; Calcium Channels ; Connexin 30/genetics ; Connexin 30/metabolism ; Ethidium/metabolism ; Gap Junctions/physiology ; Humans ; Ion Channel Gating ; Ions/metabolism ; Permeability ; Xenopus laevis/genetics
Chemical Substances	Calcium Channels ; Connexin 30 ; Ions ; Ethidium (EN464416SI)
Language	English
Publishing date	2017-10-05
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2997-x
ISSN	1083-351X ; 0021-9258
ISSN (online)	1083-351X
ISSN	0021-9258
DOI	10.1074/jbc.M117.805986
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Article ; Online: Connexin Hemichannels in Astrocytes: An Assessment of Controversies Regarding Their Functional Characteristics.

Nielsen, Brian Skriver / Hansen, Daniel Bloch / Ransom, Bruce R / Nielsen, Morten Schak / MacAulay, Nanna

Neurochemical research

2017 Volume 42, Issue 9, Page(s) 2537–2550

Abstract: Astrocytes in the mammalian central nervous system are interconnected by gap junctions made from connexins of the subtypes Cx30 and Cx43. These proteins may exist as hemichannels in the plasma membrane in the absence of a 'docked' counterpart on the ... ...

Abstract	Astrocytes in the mammalian central nervous system are interconnected by gap junctions made from connexins of the subtypes Cx30 and Cx43. These proteins may exist as hemichannels in the plasma membrane in the absence of a 'docked' counterpart on the neighboring cell. A variety of stimuli are reported to open the hemichannels and thereby create a permeation pathway through the plasma membrane. Cx30 and Cx43 have, in their hemichannel configuration, been proposed to act as ion channels and membrane pathways for different molecules, such as fluorescent dyes, ATP, prostaglandins, and glutamate. Published studies about astrocyte hemichannel behavior, however, have been highly variable and/or contradictory. The field of connexin hemichannel research has been complicated by great variability in the experimental preparations employed, a lack of highly specific pharmacological inhibitors and by confounding changes associated with genetically modified animal models. This review attempts to critically assess the gating, inhibition and permeability of astrocytic connexin hemichannels and proposes that connexins in their hemichannel configuration act as gated pores with isoform-specific permeant selectivity. We expect that some, or all, of the controversies discussed here will be resolved by future research and sincerely hope that this review serves to motivate such clarifying investigations.
MeSH term(s)	Amyloid beta-Peptides/metabolism ; Amyloid beta-Peptides/pharmacology ; Animals ; Astrocytes/drug effects ; Astrocytes/metabolism ; Cell Membrane/drug effects ; Cell Membrane/metabolism ; Connexins/agonists ; Connexins/antagonists & inhibitors ; Connexins/physiology ; Fluorescent Dyes/metabolism ; Fluorescent Dyes/pharmacology ; Humans ; Ion Channel Gating/drug effects ; Ion Channel Gating/physiology ; Peptide Fragments/metabolism ; Peptide Fragments/pharmacology
Chemical Substances	Amyloid beta-Peptides ; Connexins ; Fluorescent Dyes ; Peptide Fragments ; amyloid beta-protein (25-35)
Language	English
Publishing date	2017-09
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	199335-5
ISSN	1573-6903 ; 0364-3190
ISSN (online)	1573-6903
ISSN	0364-3190
DOI	10.1007/s11064-017-2243-7
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Article ; Online: Acute intramyocardial lipid accumulation in rats does not slow cardiac conduction per se.

Jensen, Christa F / Bartels, Emil D / Braunstein, Thomas H / Nielsen, Lars B / Holstein-Rathlou, Niels-Henrik / Axelsen, Lene N / Nielsen, Morten Schak

Physiological reports

2019 Volume 7, Issue 7, Page(s) e14049

Abstract: Diabetic patients suffer from both cardiac lipid accumulation and an increased risk of arrhythmias and sudden cardiac death. This correlation suggests a link between diabetes induced cardiac steatosis and electrical abnormalities, however, the underlying ...

Abstract	Diabetic patients suffer from both cardiac lipid accumulation and an increased risk of arrhythmias and sudden cardiac death. This correlation suggests a link between diabetes induced cardiac steatosis and electrical abnormalities, however, the underlying mechanism remains unknown. We previously showed that cardiac conduction velocity slows in Zucker diabetic fatty rats and in fructose-fat fed rats, models that both exhibit prominent cardiac steatosis. The aim of this study was to investigate whether acute cardiac lipid accumulation reduces conduction velocity per se. Cardiac lipid accumulation was induced acutely by perfusing isolated rat hearts with palmitate-glucose buffer, or subacutely by fasting rats overnight. Subsequently, longitudinal cardiac conduction velocity was measured in right ventricular tissue strips, and intramyocardial triglyceride and lipid droplet content was determined by thin layer chromatography and BODIPY staining, respectively. Perfusion with palmitate-glucose buffer significantly increased intramyocardial triglyceride levels compared to perfusion with glucose (2.16 ± 0.17 (n = 10) vs. 0.92 ± 0.33 nmol/mg WW (n = 9), P < 0.01), but the number of lipid droplets was very low in both groups. Fasting of rats, however, resulted in both significantly elevated intramyocardial triglyceride levels compared to fed rats (3.27 ± 0.43 (n = 10) vs. 1.45 ± 0.24 nmol/mg WW (n = 10)), as well as a larger volume of lipid droplets (0.60 ± 0.13 (n = 10) vs. 0.21 ± 0.06% (n = 10), P < 0.05). There was no significant difference in longitudinal conduction velocity between palmitate-glucose perfused and control hearts (0.77 ± 0.025 (n = 10) vs. 0.75 m/sec ± 0.029 (n = 9)), or between fed and fasted rats (0.75 ± 0.042 m/sec (n = 10) vs. 0.79 ± 0.047 (n = 10)). In conclusion, intramyocardial lipid accumulation does not slow cardiac longitudinal conduction velocity per se. This is true for both increased intramyocardial triglyceride content, induced by palmitate-glucose perfusion, and increased intramyocardial triglyceride and lipid droplet content, generated by fasting.
MeSH term(s)	Animals ; Heart/drug effects ; Heart Conduction System/drug effects ; Heart Conduction System/physiology ; Male ; Myocardium/metabolism ; Palmitic Acid/pharmacology ; Rats ; Rats, Sprague-Dawley ; Triglycerides/metabolism
Chemical Substances	Triglycerides ; Palmitic Acid (2V16EO95H1)
Language	English
Publishing date	2019-03-22
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2724325-4
ISSN	2051-817X ; 2051-817X
ISSN (online)	2051-817X
ISSN	2051-817X
DOI	10.14814/phy2.14049
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Article ; Online: Synopsis of the International Gap Junction Conference in Elsinore, Denmark August 5-9, 2007.

Willecke, Klaus / Nielsen, Morten Schak

Cell communication & adhesion

2007 Volume 14, Issue 6, Page(s) 251–257

Abstract: This synopsis covers the main results and conclusions from the platform presentations during the International Gap Junction Conference. More detailed information is provided in the mini reviews on controversial scientific issues, short reports of ... ...

Abstract	This synopsis covers the main results and conclusions from the platform presentations during the International Gap Junction Conference. More detailed information is provided in the mini reviews on controversial scientific issues, short reports of research results and conference abstracts published in this issue of Cell Communication and Adhesion.
MeSH term(s)	Cell Communication ; Gap Junctions ; Humans
Language	English
Publishing date	2007-11
Publishing country	England
Document type	Journal Article
ZDB-ID	2065474-1
ISSN	1543-5180 ; 1061-5385 ; 1541-9061
ISSN (online)	1543-5180
ISSN	1061-5385 ; 1541-9061
DOI	10.1080/15419060801891000
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