The rate and anisotropy of impulse propagation in the postnatal terminal crest are correlated with remodeling of Cx43 gap junction pattern

Background: Disruptions to intermyocyte coupling have been implicated in ar rhythmogenesis and development of conduction disturbances. Ar present, unde rstanding of the relationship between the microscopic organization of inter cellular coupling and the macroscopic spread of impulse in the normal and d iseased heart is largely confined to theoretical analyses. Methods and resu lts: The abundance and arrangement of gap junctions, as well as conduction properties. were assessed in terminal crest preparations isolated from the atria of neonate, weanling, and adult rabbits. We report that the connexin composition of terminal crest was uncomplicated, with Cx43 being the most p rominent isoform detectable by Western blotting and immunostaining. Termina l crest myocytes showed little change in total Cx43-gap junction per cell d uring postnatal growth as assessed by stereology. However, marked non-unifo rmities emerged in the sarcolemmal distribution of Cx43-gap junctions. Cx43 -gap junction area at myocyte termini increased 3.5-fold from birth to adul thood. Correlated with this change in Cx43, impulse propagation velocity pa rallel to the myofiber axis, as assessed by multi-site optical mapping usin g voltage-sensitive dye (di-4-ANEPPS), increased 2.4-fold. Conversely, the amount of Cx43-gap junctions on myocyte sides, and the conduction velocity transverse to the myofiber axis, remained relatively invariant during matur ation. Hence, the increasing electrical anisotropy of maturing terminal cre st was wholly accounted for by increases in conductance velocity along the bundle. This increase in longitudinal conduction velocity was correlated wi th changes in the sarsolemmal pattern, but not the overall density, of Cx43 -gap junctions. Conclusions: This study provides the first correlative stru cture/function analysis of the relationship between the macroscopic conduct ion of impulse and the microscopic cellular organization of gap junctions i n a differentiating cardiac bundle. Confirmation is provided for theoretica l predictions which emphasize the importance of the cell-to-cell geometry o f coupling in determining the spread and pattern of myocardial activation. (C) 2000 Published by Elsevier Science B.V. All rights reserved.