Slow Conduction in Cardiac Tissue, I: Effects of a Reduction of Excitability Versus a Reduction of Electrical Coupling on Microconduction
Open accessAbstract
Abstract —It was the aim of this study to characterize the spread of activation at the cellular level in cardiac tissue during conduction slowing, a key element of reentrant arrhythmias; therefore, activation patterns were assessed at high spatiotemporal resolution in narrow (70 to 80 μm) and wide (230 to 270 μm) linear strands of cultured neonatal rat ventricular myocytes, using multiple site optical recording of transmembrane voltage. Slow conduction was induced by graded elevation of [K + ] o , by applying tetrodotoxin, or by exposing the preparations to the gap junctional uncouplers palmitoleic acid or 1-octanol. The main findings of the study are 4-fold: (1) gap junctional uncoupling reduced conduction velocity (range, 37 to 47 cm/s under control conditions) to a substantially larger extent before block (≤1 cm/s; ultra-slow conduction) than did a reduction of excitability (range, ≈10 to 15 cm/s); (2) activation wavefronts during uncoupling meandered within the boundaries of the preparations, resulting in a pronounced additional slowing of conduction in wide cell strands; (3) at the cellular level, propagation during uncoupling-induced ultra-slow conduction was sustained by sequentially activated tissue patches, each of which consisted of a few cells being activated simultaneously; and (4) depending on the uncoupler used, maximal action potential upstroke velocities during ultra-slow conduction were either slightly (palmitoleic acid) or highly (1-octanol) depressed. Thus, depolarizing inward currents, the spatial pattern and degree of gap junctional coupling, and geometrical factors all contribute in a concerted manner to conduction slowing, which, at its extreme (0.25 cm/s measured over 1 mm), can reach values low enough to permit, theoretically, reentrant excitation to occur in minuscule areas of cardiac tissue (≪1 mm 2 ).
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These propagation velocities are comparable to those observed in tissues composed of immature cells where cell geometry, calcium handling, gap junction expression and spatial distribution limit conduction velocity compared to mature tissues.
“These values are comparable to those observed in tissues composed of immature cells where cell geometry, calcium handling, gap junction expression and spatial distribution, as well as other factors limit the conduction velocity when compared to mature tissues52,53.”
From A tissue-engineered scale model of the heart ventricle (2018) · cites this paper as [52]
The Abstract reports conduction velocities in cultured neonatal rat ventricular myocytes and identifies gap-junction coupling and geometry as contributors to slowing. The Minimal Pathlengths Supporting Reentrant Excitation section compares neonatal and adult cell length and gap-junction placement, but does not establish that these features, or calcium handling, make immature tissue conduct more slowly than mature tissue. Its discussion of cell length even predicts slightly higher velocities in cultured cells at a given stage of uncoupling. (LLM, conf=0.86)
Experimental — accuracy not yet measuredThese conduction velocity values were consistent with previous reports of in vitro tissues composed of immature cardiomyocytes, where factors such as geometry, calcium handling, and gap junction expression can influence CV.
“These values were consistent with previous reports of in vitro tissues composed of immature cardiomyocytes, where factors such as geometry, calcium handling, and gap junction expression can influence CV (24, 34, 35).”
From Recreating the heart's helical structure-function relationship with focused rotary jet spinning (2022) · cites this paper as [34]
The Abstract (page unavailable) reports conduction velocities in cultured neonatal rat ventricular myocyte strands, and the discussion of gap-junctional uncoupling (page unavailable) links conduction slowing to cell coupling and calcium current. The paper also discusses strand geometry, but it does not specifically establish that calcium handling influences conduction velocity. The citing paper’s own velocity values are not supplied here, so their numerical consistency cannot be checked. (LLM, conf=0.82)
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A tissue-engineered scale model of the heart ventricle
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Recreating the heart's helical structure-function relationship with focused rotary jet spinning
Chang, H., Liu, Q., Zimmerman, J. F., Lee, K. Y., Jin, Q., Peters, M. M., Rosnach, M., Choi, S., Kim, S. L., Ardoña, H. A. M., et al. (2022) · Science · doi:10.1126/science.abl6395 · Cited by 131 · see citing works
- Authors
- Rohr, S., Kucera, J. P., & Kléber, A. G.
- Affiliations
- University of Bern (CH)
- From the Department of Physiology, University of Bern, Bühlplatz 5, CH-3012 Bern, Switzerland.
- ORCID
- Rohr, Stephan
- Venue
- Circulation Research
- Published
- 1998-10-19
- Volume
- 83
- Issue
- 8
- Pages
- 781-794
- ISSN
- 0009-7330 (ISSN-L)
- 1524-4571
- OpenAlex
- W2150674116
- Cited by
- 271
- References
- 58
- Citations by year
- 2026: 5 · 2025: 6 · 2024: 10 · 2023: 4 · 2022: 6 · 2021: 7 · 2020: 11 · 2019: 6 · 2018: 10 · 2017: 4 · 2016: 9 · 2015: 10 · 2014: 16 · 2013: 5 · 2012: 11
- FWCI
- 8.43
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Circulation Research (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Science Foundation
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac electrophysiology and arrhythmias
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Connexins and lens biology
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Arrhythmias and Treatments
- Keywords
- slow conduction, reentrant arrhythmias, ventricular myocytes, action potential upstroke velocity, tetrodotoxin, extracellular potassium, palmitoleic acid, 1-octanol, conduction velocity
- MeSH terms
- Action Potentials, Animals, Animals, Newborn, Cells, Cultured, Coloring Agents, Electric Conductivity, Electric Stimulation, Extracellular Space, Heart, Myocardium, Potassium, Tetrodotoxin, Rats, Wistar, Gap Junctions, Muscle Fibers, Skeletal, Rats
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