Evidence for two types of rat liver microsomes with differing permeability to glucose and other small molecules

Radioisotope flux measurements using Millipore filtration revealed two populations of rat liver microsomes designated type A and B. Type A and B vesicle are similar in that both are essentially impermeable to sucrose yet permeable to Cl-. About 70% of the microsome (type A) are permeable to D-glucose, L-glucose, 2-deoxy-D-glucose, D-mannose, D-mannitol, uridine, glycine, L-leucine, choline+, Tris+, Rb+, K+, and Na+. Other solutes such as D-gluconate-, D-glucosamine+, N-acetyl-D-glucosamine, L-glutamate-, L-lysine+, sulfate2-, oxalate2-, and phosphate anions transverse type A vesicles with an intermediate rate. All of the above solutes except Cl- pass with a comparatively slow rate the remaining 30% type B vesicles. Both type A and B microsomes are relatively impermeable to glucose 6-phosphate and related monophosphates. Membrane potential measurements using liver microsomes and control membrane vesicles derived from rabbit skeletal muscle sarcoplasmic reticulum indicated that type A liver microsomes, despite being permeable to K+ and Na+, either lack or contain only a small number of highly conducting K+ and Na+ structures, such as the K,Na channel of sarcoplasmic reticulum. Treatment with the anion transport inhibitor 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid lowered the permeability of type A vesicles to several uncharged and negatively charged solutes including D-glucose and gluconate-. These results suggest that a large fraction of liver microsomes is rendered permeable to various biologically relevant solutes and ions, perhaps through the presence of one or more channels with a maximal diameter of approximately 7-8 A which select(s) against solutes on the basis of their size and charge.