PMID- 28588504
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20200929
IS  - 1664-042X (Print)
IS  - 1664-042X (Electronic)
IS  - 1664-042X (Linking)
VI  - 8
DP  - 2017
TI  - TNFalpha Modulates Cardiac Conduction by Altering Electrical Coupling between 
      Myocytes.
PG  - 334
LID - 10.3389/fphys.2017.00334 [doi]
LID - 334
AB  - Background: Tumor Necrosis Factor alpha (TNFalpha) upregulation during acute inflammatory 
      response has been associated with numerous cardiac effects including modulating 
      Connexin43 and vascular permeability. This may in turn alter cardiac gap 
      junctional (GJ) coupling and extracellular volume (ephaptic coupling) 
      respectively. We hypothesized that acute exposure to pathophysiological TNFalpha 
      levels can modulate conduction velocity (CV) in the heart by altering electrical 
      coupling: GJ and ephaptic. Methods and Results: Hearts were optically mapped to 
      determine CV from control, TNFalpha and TNFalpha + high calcium (2.5 vs. 1.25 mM) treated 
      guinea pig hearts over 90 mins. Transmission electron microscopy was performed to 
      measure changes in intercellular separation in the gap junction-adjacent 
      extracellular nanodomain-perinexus (W(P)). Cx43 expression and phosphorylation 
      were determined by Western blotting and Cx43 distribution by confocal 
      immunofluorescence. At 90 mins, longitudinal and transverse CV (CV(L) and CV(T), 
      respectively) increased with control Tyrode perfusion but TNFalpha slowed CV(T) alone 
      relative to control and anisotropy of conduction increased, but not 
      significantly. TNFalpha increased W(P) relative to control at 90 mins, without 
      significantly changing GJ coupling. Increasing extracellular calcium after 30 
      mins of just TNFalpha exposure increased CV(T) within 15 mins. TNFalpha + high calcium 
      also restored CV(T) at 90 mins and reduced W(P) to control values. Interestingly, 
      TNFalpha + high calcium also improved GJ coupling at 90 mins, which along with 
      reduced W(P) may have contributed to increasing CV. Conclusions: Elevating 
      extracellular calcium during acute TNFalpha exposure reduces perinexal expansion, 
      increases ephaptic, and GJ coupling, improves CV and may be a novel method for 
      preventing inflammation induced CV slowing.
FAU - George, Sharon A
AU  - George SA
AD  - Department of Biomedical Engineering and Sciences, Virginia Polytechnic Institute 
      and State UniversityBlacksburg, VA, United States.
FAU - Calhoun, Patrick J
AU  - Calhoun PJ
AD  - Department of Biological Sciences, Virginia Polytechnic Institute and State 
      UniversityBlacksburg, VA, United States.
FAU - Gourdie, Robert G
AU  - Gourdie RG
AD  - Department of Biomedical Engineering and Sciences, Virginia Polytechnic Institute 
      and State UniversityBlacksburg, VA, United States.
AD  - Center for Heart and Regenerative Medicine, Virginia Tech Carilion Research 
      InstituteRoanoke, VA, United States.
FAU - Smyth, James W
AU  - Smyth JW
AD  - Center for Heart and Regenerative Medicine, Virginia Tech Carilion Research 
      InstituteRoanoke, VA, United States.
FAU - Poelzing, Steven
AU  - Poelzing S
AD  - Department of Biomedical Engineering and Sciences, Virginia Polytechnic Institute 
      and State UniversityBlacksburg, VA, United States.
AD  - Center for Heart and Regenerative Medicine, Virginia Tech Carilion Research 
      InstituteRoanoke, VA, United States.
LA  - eng
GR  - R01 HL056728/HL/NHLBI NIH HHS/United States
PT  - Journal Article
DEP - 20170523
PL  - Switzerland
TA  - Front Physiol
JT  - Frontiers in physiology
JID - 101549006
PMC - PMC5440594
OTO - NOTNLM
OT  - TNFalpha
OT  - calcium
OT  - conduction
OT  - connexin43
OT  - ephaptic coupling
EDAT- 2017/06/08 06:00
MHDA- 2017/06/08 06:01
PMCR- 2017/05/23
CRDT- 2017/06/08 06:00
PHST- 2017/03/30 00:00 [received]
PHST- 2017/05/08 00:00 [accepted]
PHST- 2017/06/08 06:00 [entrez]
PHST- 2017/06/08 06:00 [pubmed]
PHST- 2017/06/08 06:01 [medline]
PHST- 2017/05/23 00:00 [pmc-release]
AID - 10.3389/fphys.2017.00334 [doi]
PST - epublish
SO  - Front Physiol. 2017 May 23;8:334. doi: 10.3389/fphys.2017.00334. eCollection 
      2017.