Abstract
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.
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