Label-free conduction velocity mapping and gap junction assessment of functional iPSC-Cardiomyocyte monolayers

The propagation and coordination of lymphatic contractions were studied in the mesentery of the rat small intestine using in situ microscopic observation. Indexes of lymphatic diameter were simultaneously measured at two adjacent lymphangions in spontaneously contracting lymphatics (n = 51). Diameter index, contraction frequency, and the percentage of the intersegmental contractions that were propagated and coordinated (PP) were determined at both sites. The conduction velocity of the contractile activity and the percentage of the coordinated contractions that were propagated both antegrade to the direction of lymph flow and retrograde to the flow stream were determined. The results indicate that 1) 80-90% of the lymphatic contractions in the vessels we evaluated were propagated, 2) the wave of contractile activity propagated both centrally and peripherally, and 3) the conduction velocity of the contractile activity was approximately 4-8 mm/s. We tested the hypothesis that gap junctional communication is responsible for the coordination of the contractile event. To accomplish this, we used the gap junction blockers n-heptanol and oleic acid. PP was 90 +/- 4% under normal conditions and fell to a minimum value of 55 +/- 7% during the gap junction blockade. These results indicate that gap junctional communication played an important role in the propagation and coordination of contractions that occurred in spontaneously active lymphatics.

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Interstitial volume modulates the conduction velocity-gap junction relationship

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00868.2011 ◽

2012 ◽

Vol 302 (1) ◽

pp. H278-H286 ◽

Cited By ~ 53

Author(s):

Rengasayee Veeraraghavan ◽

Mohamed E. Salama ◽

Steven Poelzing

Keyword(s):

Guinea Pig ◽

Gap Junction ◽

Conduction Velocity ◽

Important Determinant ◽

Cardiac Conduction ◽

Cell Width ◽

Interstitial Volume ◽

Ventricular Tachycardias ◽

The Relationship ◽

Isolated Cell

Cardiac conduction through gap junctions is an important determinant of arrhythmia susceptibility. Yet, the relationship between degrees of Gj uncoupling and conduction velocity (θ) remains controversial. Conflicting results in similar experiments are normally attributed to experimental differences. We hypothesized that interstitial volume modulates conduction velocity and its dependence on Gj. Interstitial volume (VIS) was quantified histologically from guinea pig right ventricle. Optical mapping was used to quantify conduction velocity and anisotropy (ARθ). Albumin (4 g/l) decreased histologically assessed VIS, increased transverse θ by 71 ± 10%, and lowered ARθ. Furthermore, albumin did not change isolated cell size. Conversely, mannitol increased VIS, decreased transverse θ by 24 ± 4%, and increased ARθ. Mannitol also decreased cell width by 12%. Furthermore, mannitol was associated with spontaneous ventricular tachycardias in three of eight animals relative to zero of 15 during control. The θ-Gj relationship was assessed using the Gj uncoupler carbenoxolone (CBX). Whereas 13 μM CBX did not significantly affect θ during control, it slowed transverse θ by 38 ± 9% during mannitol (edema). These data suggest changes in VIS modulate θ, ARθ, and the θ-Gj relationship and thereby alter arrhythmia susceptibility. Therefore, VIS may underlie arrhythmia susceptibility, particularly in diseases associated with gap junction remodeling.

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Gap junction modifier rotigaptide decreases the susceptibility to ventricular arrhythmia by enhancing conduction velocity and suppressing discordant alternans during therapeutic hypothermia in isolated rabbit hearts

Heart Rhythm ◽

10.1016/j.hrthm.2015.07.023 ◽

2016 ◽

Vol 13 (1) ◽

pp. 251-261 ◽

Cited By ~ 21

Author(s):

Yu-Cheng Hsieh ◽

Jiunn-Cherng Lin ◽

Chen-Ying Hung ◽

Cheng-Hung Li ◽

Shien-Fong Lin ◽

...

Keyword(s):

Ventricular Arrhythmia ◽

Gap Junction ◽

Therapeutic Hypothermia ◽

Conduction Velocity

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Conduction velocity and gap junction resistance in hypertrophied, hypoxic guinea-pig left ventricular myocardium

Experimental Physiology ◽

10.1113/expphysiol.1998.sp004157 ◽

1998 ◽

Vol 83 (6) ◽

pp. 763-770 ◽

Cited By ~ 30

Author(s):

M Cooklin ◽

WR Wallis ◽

DJ Sheridan ◽

CH Fry

Keyword(s):

Guinea Pig ◽

Gap Junction ◽

Conduction Velocity ◽

Ventricular Myocardium ◽

Left Ventricular ◽

Left Ventricular Myocardium ◽

Junction Resistance

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Gap junction heterogeneity as mechanism for electrophysiologically distinct properties across the ventricular wall

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00887.2009 ◽

2010 ◽

Vol 298 (3) ◽

pp. H787-H794 ◽

Cited By ~ 22

Author(s):

Maria Strom ◽

Xiaoping Wan ◽

Steven Poelzing ◽

Eckhard Ficker ◽

David S. Rosenbaum

Keyword(s):

Left Ventricle ◽

Gap Junction ◽

Conduction Velocity ◽

Velocity Dispersion ◽

Expression Patterns ◽

Fold Increase ◽

Ventricular Wall ◽

Cx43 Expression ◽

Electrophysiological Properties ◽

Junction Protein

Gap junctions are critical to maintaining synchronized impulse propagation and repolarization. Heterogeneous expression of the principal ventricular gap junction protein connexin43 (Cx43) is associated with action potential duration (APD) dispersion across the anterior ventricular wall. Little is known about Cx43 expression patterns and their disparate impact on regional electrophysiology throughout the heart. We aimed to determine whether the anterior and posterior regions of the heart are electrophysiologically distinct. Multisegment, high-resolution optical mapping was performed in canine wedge preparations harvested separately from the anterior left ventricle (aLV; n = 8) and posterior left ventricle (pLV; n = 8). Transmural APD dispersion was significantly greater on the aLV than the pLV (45 ± 13 vs. 26 ± 8.0 ms; P < 0.05). Conduction velocity dispersion was also significantly higher ( P < 0.05) across the aLV (39 ± 7%) than the pLV (16 ± 3%). Carbenoxolone perfusion significantly enhanced APD and conduction velocity dispersion on the aLV (by 1.53-fold and 1.36-fold, respectively), but not the pLV (by 1.27-fold and 1.2-fold, respectively), and produced a 4.2-fold increase in susceptibility to inducible arrhythmias in the aLV. Confocal immunofluorescence microscopy revealed significantly ( P < 0.05) greater transmural dispersion of Cx43 expression on the aLV (44 ± 10%) compared with the pLV wall (8.3 ± 0.7%), suggesting that regional expression of Cx43 expression patterns may account for regional electrophysiological differences. Computer simulations affirmed that localized uncoupling at the epicardial-midmyocardial interface is sufficient to produce APD gradients observed on the aLV. These data demonstrate that the aLV and pLV differ importantly with respect to their electrophysiological properties and Cx43 expression patterns. Furthermore, local underexpression of Cx43 is closely associated with transmural electrophysiological heterogeneity on the aLV. Therefore, regional and transmural heterogeneous Cx43 expression patterns may be an important mechanism underlying arrhythmia susceptibility, particularly in disease states where gap junction expression is altered.

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Regional gap junction inhibition increases defibrillation thresholds

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.01074.2002 ◽

2003 ◽

Vol 285 (1) ◽

pp. H10-H16 ◽

Cited By ~ 12

Author(s):

J. Jason Sims ◽

Kell L. Schoff ◽

Jennifer M. Loeb ◽

Nicholas A. Wiegert

Keyword(s):

Ventricular Fibrillation ◽

Gap Junction ◽

Conduction Velocity ◽

Velocity Dispersion ◽

Important Determinant ◽

Refractory Periods ◽

Regional Gap ◽

Junction Conductance ◽

Regional Infusion ◽

Gap Junction Inhibition

It is clear that ischemia inhibits successful defibrillation by altering regional electro-physiology. However, the exact mechanisms are unclear. This study investigated whether regional gap junction inhibition increases biphasic shock defibrillation thresholds (DFT). Sixteen swine were instrumented with a mid-left anterior descending (LAD) perfusion catheter for regional infusion of 0.5 mM/h heptanol ( n = 8) or saline ( n = 8). DFT values and effective refractory periods (ERP) at five myocardial sites were determined. Regional conduction velocity (CV) was determined in an LAD drug-perfused and nondrug-perfused region in an additional seven swine. Regional heptanol infusion increased 50% DFT values by 33% ( P = 0.01) and slowed CV by 42–59% ( P < 0.01) but did not affect ERP. Regional heptanol also increased CV dispersion by ∼270% ( P < 0.05) but did not change ERP dispersion. Regional placebo did not alter any of these parameters. Furthermore, regional heptanol infusion induced spontaneous ventricular fibrillation in eight of eight animals. Increasing spatial conduction velocity dispersion by impairing regional gap junction conductance increased DFT values. Dispersion in conduction velocity slowing during regional ischemia may be an important determinant of defibrillation efficacy.

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