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Related Concept Videos

Desmosomes01:05

Desmosomes

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The term desmosome derives from the Greek words "desmo" and "soma" meaning "adhesion bodies." This structure was first observed during the late 1800s and described as small, dense nodules in the epidermis. Desmosomes are button-like structures that help form an interlinked network of intermediate filaments across the cells. These junctions are  essential to hold cells together under mechanical stress and to maintain tissue integrity. Desmosomes are multi-protein...
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Conduction System of the Heart01:20

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The cardiac conduction system produces and transmits electrical impulses that prompt myocardial contraction, ensuring efficient heart function. This intricate system ensures that the heart beats in a coordinated and efficient manner, beginning with the atria and then the ventricles. The conduction system optimizes cardiac output by maintaining this precise sequence, which is crucial for adequate blood circulation.
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Conduction System of the Heart01:19

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Autorhythmicity is a term that refers to the heart's inherent ability to generate electrical signals and instigate muscle contractions. This self-regulating conduction system within the heart consists of two key components: the pacemaker cells and specialized conducting cells.
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Anchoring Junctions01:03

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Anchoring junctions are multiprotein complexes that help cells connect to other cells and the extracellular matrix. Anchoring junctions are present on the lateral and basal surfaces of cells, providing strong and flexible connections. Focal adhesions are often formed due to cell interactions with the ECM substrata, which initiate signal transduction via kinase cascades and other mechanisms. Together, they provide stability and tissue integrity. There are three types of anchoring junctions:...
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Contact-dependent Signaling01:19

Contact-dependent Signaling

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Contact-dependent signaling, as the name suggests, requires that communicating cells be in direct contact with each other. This is achieved either through receptor-ligand interactions or by specialized cytoplasmic channels that allow the flow of small molecules between cells. In animal cells, channels called gap junctions facilitate contact-dependent signaling in certain tissues, whereas, plasmodesmata perform a similar function in plants.
Gap Junctions
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Adherens Junctions01:24

Adherens Junctions

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Strong contact points between adjacent cells anchor them to each other, forming tissues. Such anchoring junctions are of two types –  adherens junctions and desmosomes. Adherens junctions are abundant in tissues such as  epithelium and endothelium, forming a continuous zone of adhesion called the adhesion belt. In other tissues, such as  heart muscle, they appear as clusters, linking the cells to produce coordinated heart muscle contraction.
Adherens Junctions are Dynamic
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Methods for the Isolation, Culture, and Functional Characterization of Sinoatrial Node Myocytes from Adult Mice
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Methods for the Isolation, Culture, and Functional Characterization of Sinoatrial Node Myocytes from Adult Mice

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Desmosomal junctions are necessary for adult sinus node function.

Valeria Mezzano1, Yan Liang1, Adam T Wright2

  • 1Department of Medicine, University of California-San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0613C, USA.

Cardiovascular Research
|April 22, 2016
PubMed
Summary
This summary is machine-generated.

Desmosomes, previously thought only for structure, are crucial for cardiac pacemaker function. Loss of desmoplakin (DSP) disrupts heart rhythm, revealing a new mechanism for sinus node disease.

Keywords:
Arrhythmia (mechanisms)DesmosomeHeart rate variabilityPhysiology/functionSinus node dysfunction

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Area of Science:

  • Cardiovascular Biology
  • Cellular Cardiology
  • Molecular Mechanisms of Cardiac Function

Background:

  • Cardiac pacemaker function traditionally focuses on ion and gap junction channels.
  • Pacemaker cells possess desmosomes, cell adhesion structures, whose role in pacemaker activity is unexplored.

Purpose of the Study:

  • To investigate the role of desmosomes in cardiac pacemaker function.
  • To elucidate the contribution of desmoplakin (DSP), a key desmosomal protein, to sinoatrial node (SAN) activity.

Main Methods:

  • Generated a cardiac conduction-specific desmoplakin knockout (csKO) mouse model (Hcn4-Cre-ERT2; DSP f/f).
  • Analyzed adult DSP csKO mice and a patient with a pathogenic DSP variant.
  • Utilized in vivo, ex vivo (intact atria), and in vitro (cardiomyocytes) approaches.

Main Results:

  • Desmosomal dysregulation, specifically DSP loss, caused increased sinus pauses and sinus node dysfunction without cardiomyopathy.
  • DSP csKO mice exhibited impaired beat-to-beat regulation and migrating pacemaker sites linked to connexin 45 loss.
  • In vitro studies confirmed DSP loss impacts beat-to-beat regulation in cardiomyocytes.

Conclusions:

  • Desmosomes play an essential, previously unrecognized role in cardiac pacemaker function.
  • This finding provides a novel mechanism for understanding beat-to-beat regulation and sinus node diseases.
  • Highlights the importance of desmosomal integrity for maintaining normal heart rhythm.