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Circulation Research. 1998;83:781-794

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(Circulation Research. 1998;83:781-794.)
© 1998 American Heart Association, Inc.


Original Contributions

Slow Conduction in Cardiac Tissue, I

Effects of a Reduction of Excitability Versus a Reduction of Electrical Coupling on Microconduction

Stephan Rohr, Jan P. Kucera, , André G. Kléber

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

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, {approx}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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