Characterization of impulse propagation at the microscopic level across geometrically defined expansions of excitable tissue: multiple site optical recording of transmembrane voltage (MSORTV) in patterned growth heart cell cultures.

Abstract

Impulse propagation across sudden expansions of excitable tissue has been shown to exhibit various forms of conduction disturbance on a macroscopic scale, ranging from small delays to unidirectional or complete conduction block. With the present study, we attempted to characterize systematically the dependence of impulse propagation on the geometry of the underlying excitable tissue on a microscopic scale by investigating the spatio-temporal pattern of transmembrane voltage changes associated with impulse propagation from a narrow cell strand to a large cell area using multiple site optical recording of transmembrane voltage (MSORTV) in conjunction with patterned growth of neonatal rat heart cells in culture. While action potential propagation was smooth in the case of funneled expansions, delays of variable size occurred during propagation into rectangular or incised expansions. Close to the abrupt expansion, which functionally represented an increased electrical load to the narrow cell strand, the delays were accompanied by marked distortions of the action potential upstroke, exhibiting, in extreme cases, an initial depolarization to 50% followed by a delayed secondary depolarization to 100% of the full-signal amplitude. These distortions, which were based on bidirectional electrotonic interactions across the transition, were maximal immediately downstream from the expansion. The maximal slowing of impulse conduction across abrupt expansions was, in agreement with recently published results obtained from two-dimensional computer simulations, always situated in the expanded region. At high stimulation rates, the delays sometimes turned into intermittent unidirectional blocks, as revealed by reverse stimulation. These blocks were always characterized by a marked abbreviation of the action potentials upstream from the region causing the block which might, in an appropriate network, facilitate reentry because of the associated shortening of the refractory period. Because the patterns were composed of cells having identical membrane properties, the results show that the local action potential shape can be modulated profoundly by the two-dimensional architecture of the underlying cell ensemble alone.