Evidence of specialized tissue in human interatrial septum: histological, immunohistochemical and ultrastructural findings

PLoS One. 2014 Nov 20;9(11):e113343. doi: 10.1371/journal.pone.0113343. eCollection 2014.

Abstract

Background: There is a paucity of information on structural organization of muscular bundles in the interatrial septum (IAS). The aim was to investigate histologic and ultrastructural organization of muscular bundles in human IAS, including fossa ovalis (FO) and flap valve.

Methods: Macroscopic and light microscopy evaluations of IAS were performed from postmortem studies of 40 patients. Twenty three IAS specimens underwent serial transverse sectioning, and 17--longitudinal sectioning. The transverse sections from 10 patients were immunolabeled for HCN4, Caveolin3 and Connexin43. IAS specimens from 6 other patients underwent electron microscopy.

Results: In all IAS specimens sections the FO, its rims and the flap valve had muscle fibers consisting of working cardiac myocytes. Besides the typical cardiomyocytes there were unusual cells: tortuous and horseshoe-shaped intertangled myocytes, small and large rounded myocytes with pale cytoplasm. The cells were aggregated in a definite structure in 38 (95%) cases, which was surrounded by fibro-fatty tissue. The height of the structure on transverse sections positively correlated with age (P = 0.03) and AF history (P = 0.045). Immunohistochemistry showed positive staining of the cells for HCN4 and Caveolin3. Electron microscopy identified cells with characteristics similar to electrical conduction cells.

Conclusions: Specialized conduction cells in human IAS have been identified, specifically in the FO and its flap valve. The cells are aggregated in a structure, which is surrounded by fibrous and fatty tissue. Further investigations are warranted to explore electrophysiological characteristics of this structure.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Atrial Septum / metabolism
  • Atrial Septum / pathology*
  • Atrial Septum / ultrastructure
  • Caveolin 3 / immunology
  • Caveolin 3 / metabolism
  • Connexin 43 / immunology
  • Connexin 43 / metabolism
  • Female
  • Heart Valves / metabolism
  • Heart Valves / pathology
  • Heart Valves / ultrastructure
  • Humans
  • Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels / immunology
  • Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels / metabolism
  • Immunohistochemistry
  • Longitudinal Studies
  • Male
  • Microscopy, Electron
  • Middle Aged
  • Muscle Proteins / immunology
  • Muscle Proteins / metabolism
  • Potassium Channels / immunology
  • Potassium Channels / metabolism

Substances

  • Caveolin 3
  • Connexin 43
  • HCN4 protein, human
  • Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels
  • Muscle Proteins
  • Potassium Channels

Grants and funding

This work has been supported by the Russian Federation State Task program for the Almazov Centre 2012-2014#4. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.