Modelling depolarization delay, sodium currents, and electrical potentials in cardiac transverse tubules

T-tubules are invaginations of the lateral membrane of striated muscle cells that provide a large surface for ion channels and signaling proteins, thereby supporting excitation-contraction coupling. T-tubules are often remodeled in heart failure. To better understand electrical behavior of T-tubules of cardiac cells in health and disease, this study addresses two largely unanswered questions regarding their electrical properties: (1) the delay of T-tubular membrane depolarization and (2) the effects of T-tubular sodium current on T-tubular potentials. Here, we present a simple computational model to determine the delay in depolarization of deep T-tubular membrane segments as the narrow T-tubular lumen provides resistance against the extracellular current. We compare healthy and diseased tubules from mouse and human, and conclude that diseased T-tubules depolarize even faster than healthy ones due to tubule widening. We moreover model the effect of a large T-tubular sodium current on T-tubular potentials. We observe that extracellular potentials are slightly negative and, therefore, the sodium current is self-attenuating.Despite the simplicity of this model, these results show that (1) the excitation-contraction coupling defects seen in diseased cells cannot be explained by T-tubular remodeling alone; and (2) the self-attenuation of the sodium current resembles ephaptic effects that have been described for regions of the intercalated discs where the opposing membranes are very close together.