Original Contributions |
From the Department of Physiology, University of Bern, Bühlplatz 5, CH-3012 Bern, Switzerland.
Correspondence to Stephan Rohr, MD, Department of Physiology, University of Bern, Bühlplatz 5, CH-3012 Bern, Switzerland. E-mail rohr{at}pyl.unibe.ch
AbstractIt 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 mm2).
Key Words: impulse propagation discontinuous conduction gap junction action potential upstroke voltage-sensitive dye
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