Aqueous Diffusion Pathways as a Part of the Ventricular Cell Ultrastructure

The physical organization of the ventricular myocyte includes barriers for the movement of objects of varying dimensions ranging from ions to solid particles. There are two kinds of diffusion in the cell: lateral (in membranes) and aqueous. Here we examine the size constraints of aqueous diffusion pathways and discuss their impact on cellular physiology. Calibrated gold nanoparticles were used to probe the accessibility of the entire transverse-axial tubular system (TATS), the sarcoplasm, and intracellular structures. The TATS tubules, although up to 300 nm in diameter, permitted only particles ≤11 nm to enter. When calibrated nanoparticles were added to permeabilized ventricular cells, particles ≤11 nm were found in the sarcoplasm. The distribution of nanoparticles in the cells allowed us to conclude that 1), the TATS and the sarcoplasm are accessible only for particles ≤11 nm; 2), the gaps between T-tubules and junctional sarcoplasmic reticulum (jSR), jSR and mitochondria, and intermitochondrial contacts are inaccessible for particles with physical size >3 nm; 3), the mitochondrial voltage-dependent anion channel and the nuclear pore complex in ventricular cells could not be penetrated by particles ≥6 nm; and 4), there is a difference in size clearance between transversal and longitudinal sarcoplasmic diffusional pathways.