Anomalous ion diffusion within skeletal muscle transverse tubule networks

Using our model we found that the t-tubule network geometry reduced the K+ diffusion coefficient to 19–27% of its value in free solution, which is consistent with the experimentally observed value of 21% and is significantly smaller than existing theoretical values that range from 32–50%. We also found that diffusion in the t-tubules is anomalous for skeletal muscle fibres with a diameter of less than approximately 10–20 μm as a result of obstructed diffusion. We also observed that the [K+] within the interior of the t-tubule network during high-frequency activation is greater for fibres with a larger diameter. Smaller skeletal muscle fibres are therefore more resistant to membrane depolarization. Because the t-tubule network is anisotropic and inhomogeneous, we also found that the [K+] distribution generated within the network was irregular for fibres of small diameter.Our model explains the measured effective diffusion coefficient for ions in skeletal muscle t-tubules.Skeletal muscle fibres contain transverse tubular (t-tubule) networks that provide for rapid propagation of electrical signals into the fibre and ensures near simultaneous contraction in the constituent myofibrils. These t-tubule networks are highly branched space-filling networks that are located near sarcomere Z-lines in amphibians and the A-I junction in mammals. The t-tubule network therefore largely lies in a plane perpendicular to the axis of the muscle fibre. The electrical signals that propagate along the planar t-tubules are generated by the transport of ions across the t-tubule membranes and this can result in significant changes in ion concentrations within the t-tubules during muscle excitation. In particular, K+ ions accumulate within the t-tubule network as a result of voltage-gated K+ channels that repolarize the membrane during action potentials. This K+ accumulation can result in membrane depolarization and reduced membrane excitability as a result of Na+ channel inactivation and con