Optical measurement of cell-to-cell coupling in intact heart using subthreshold electrical stimulation

Fadi G. Akar, Bradley J. Roth, David S. Rosenbaum

Research output: Contribution to journalArticlepeer-review

Abstract

Electrical coupling between myocytes plays a critical role in propagation, repolarization, and arrhythmias. On the basis of predictions from cable theory, we hypothesized that the cardiac space constant (λ) measured from the decay of subthreshold transmembrane potential (ST-Vm) in space would provide an index of regional cell-to-cell coupling in the intact heart. With the use of voltagesensitive dyes, the distribution of ST-Vm was measured from hundreds of sites in close proximity to the site of subthreshold stimulation, λ was calculated from the exponential decay of ST-Vm in space. Consistent with known directional differences in axial resistance, the spatial distribution of ST-Vm was strongly dependent on fiber orientation, because λ was significantly (P < 0.001) longer along (1.5 ± 0.1 mm) compared with across (0.8 ± 0.1 mm) fibers. There was a close linear relationship (P < 0.001) between conduction velocity (CV) and λ along all fiber angles tested. Reducing gap junctional conductance by heptanol reversibly decreased CV and λ in parallel by ∼50%. In contrast, sodium channel blockade by flecainide slowed CV by 40% but had no effect on λ, reaffirming that λ was an index of passive but not active membrane properties. These data establish the feasibility of measuring λ as an index of cell-to-cell coupling in the intact heart, and indicate strong dependency of λ on fiber orientation and pharmacological alterations of gap junction conductance.

Original languageEnglish (US)
Pages (from-to)H533-H542
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume281
Issue number2 50-2
DOIs
StatePublished - 2001

Keywords

  • Arrhythmias
  • Gap junctions
  • Optical mapping
  • Space constant

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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