Cardiac transverse (t-) tubules form a complex network of membrane invaginations in mammalian ventricular myocytes, also known as the transverse-axial tubular system (TATS). Biophysically realistic computer models have been used to investigate experimental ambiguities and aspects of TATS function not currently amenable to experimental investigation: 1. Fraction of cell membrane within the TATS: Detubulation of rat ventricular myocytes causes a ~32% decrease of membrane capacitance (Despa et al., 2003) whereas optical measurements suggest ~56% of the cell membrane within the TATS (Soeller & Cannell, 1999). Analysis of factors that may account for this discrepancy, and calculation of the combinations of t-tubule radius, length and density that produce t-tubular membrane fractions of 32% or 56%, suggest that the true fraction is at the upper end of this range. 2. Electrical coupling between the surface and TATS membranes: It has long been speculated that voltage control within the TATS may be inadequate, allowing voltage escape. Analysis based on cable theory, and simulations using models in voltage and current clamp mode, show that voltage spread across both membranes and its equilibration due to their tight electrical coupling is very fast (within 20 μs); thus membrane voltage is almost homogeneous over the whole cell membrane during activity. 3. Ion diffusion within TATS: The complexity of the TATS appears to restrict ion diffusion in the TATS lumen. Simulations performed using a model of a single tubule suggest that variable diameter along the length of the tubule and ion buffers in the tubule lumen play a major role in the restricted diffusion and thus in the slowed ion exchange between the TATS lumen and extracellular space. 4. Ion concentration changes in TATS and their consequences: Recent detubulation experiments suggest that many trans-membrane ion flux pathways (for I_Ca, I_NaCa, I_NaK and others) are located predominantly within the TATS (Brette & Orchard, 2003). Incorporation of this distribution, and restricted ion diffusion between the tubular and extracellular space, into rat and guinea pig models results in changes of tubular Ca²⁺ and K⁺ concentrations during activity, which depend on stimulation rate. These changes (particularly Ca²⁺ depletion) cause a significant decrease of intracellular Ca²⁺ load and hence reduction of intracellular Ca²⁺ transients. These data suggest that the TATS may play an important role in modulating cardiac cell function.