Not yet reviewed by Pith; the record is open.

Mathematical models for excitable tissue with explicit representation of individual cells are highly detailed and can, unlike classical homogenized models, represent complex cellular geometries and local membrane variations. However, these cell-based models are challenging to approximate numerically, partly due to their mixed-dimensional nature with unknowns both in the bulk and at the lower-dimensional cellular membranes. We here develop and evaluate a novel solution strategy for the cell-based KNP-EMI model describing ionic electrodiffusion in and between intra- and extracellular compartments with explicit representation of individual cells. The strategy is based on operator splitting, a multiplier-free formulation of the coupled dynamics across sub-regions, and a discontinuous Galerkin discretization. In addition to desirable theoretical properties, such as local mass conservation, the scheme is practical as it requires no specialized functionality in the finite element assembly and order optimal solvers for the resulting linear systems can be realized with black-box algebraic multigrid preconditioners. Numerical investigations show that the proposed solution strategy is accurate, robust with respect to discretization parameters, and that the parallel scalability of the solver is close to optimal - both for idealized and realistic two and three dimensional geometries.