Effect of transverse gap-junction channels on transverse propagation in an enlarged PSpice model of cardiac muscle.
BACKGROUND
In previous PSpice modeling studies of simulated action potentials (APs) in parallel chains of cardiac muscle, it was found that transverse propagation could occur between adjacent chains in the absence of gap-junction (gj) channels, presumably by the electric field (EF) generated in the narrow interstitial space between the chains. Transverse propagation was sometimes erratic, the more distal chains firing out of order.


METHODS
In the present study, the propagation of complete APs was studied in a 2-dimensional network of 100 cardiac muscle cells (10 x 10 model). Various numbers of gj-channels (assumed to be 100 pS each) were inserted across the junctions between the longitudinal cells of each chain and between adjacent chains (only at the end cells of each chain). The shunt resistance produced by the gj-channels (Rgj) was varied from 100,000 M omega (0 gj-channels) to 1,000 M omega (10 channels), 100 M omega (100 channels) and 10 M omega (1,000 channels). Total propagation time (TPT) was measured as the difference between the times when the AP rising phase of the first cell (cell # A1) and the last cell (in the J chain) crossed 0 mV. When there were no gj-channels, the excitation was transmitted between cells by the EF, i.e., the negative potential generated in the narrow junctional clefts (e.g., 100 angstroms) when the prejunctional membrane fired an AP. For the EF mechanism to work, the prejunctional membrane must fire a fraction of a millisecond before the adjacent surface membrane. When there were many gj-channels (e.g., 100 or 1,000), the excitation was transmitted by local-circuit current flow from one cell to the next through these channels.


RESULTS
TPT was measured as a function of four different numbers of transverse gj-channels, namely 0, 10, 100 and 1,000, and four different numbers of longitudinal gj-channels, namely 0, 10, 100 and 1,000. Thus, 16 different measurements were made. It was found that increasing the number of transverse channels had no effect on TPT when the number of longitudinal channels was low (i.e., 0 or 10). In contrast, when the number of longitudinal gj-channels was high (e.g., 100 or 1,000), then increasing the number of transverse channels decreased TPT markedly.


CONCLUSIONS
Thus, complete APs could propagate along a network of 100 cardiac muscle cells even when no gj-channels were present between the cells. Insertion of transverse gj-channels greatly speeded propagation through the 10 x 10 network when there were also many longitudinal gj-channels.
Ramasamy
Lakshminarayanan
L
Dept. of Molecular & Cellular Physiology, University of Cincinnati College of Medicine, Cincinnati, OH 45267-0576, USA. laksnarayana@yahoo.com
Sperelakis
Nicholas
N
D000200:Action Potentials / Q000502:physiology; D003198:Computer Simulation; D017629:Gap Junctions / Q000378:metabolism*; D008954:Models, Biological; D008959:Models, Neurological; D009206:Myocardium / Q000378:metabolism*; D032389:Myocytes, Smooth Muscle / Q000502:physiology; D009431:Neural Conduction / Q000502:physiology; D012984:Software