Hypertonic media inhibit receptor-mediated endocytosis by blocking clathrin-coated pit formation. Two treatments, potassium depletion and hypertonic media, both inhibit endocytosis and lead to the formation of clathrin "microcages." These microcages appear as empty clathrin structures on the inner membrane surface and deplete the cytoplasm of clathrin needed for normal coated pit assembly. Hypertonic treatment causes coated pits to disappear and results in the formation of microcages, similar to potassium depletion. Both treatments lead to the loss of clathrin lattices and the dispersion of LDL receptors on the cell surface. However, upon return to normal conditions, these changes reverse, with clathrin lattices and receptor clusters reappearing. The formation of microcages is thought to be due to abnormal clathrin polymerization, possibly caused by cytoplasmic acidification. The study shows that both potassium depletion and hypertonic treatment lead to similar effects on clathrin and receptor distribution, suggesting that they inhibit endocytosis by rendering clathrin unavailable for normal coated pit assembly. The mechanisms underlying these effects are not fully understood, but the formation of microcages appears to be a key factor in the inhibition of endocytosis.Hypertonic media inhibit receptor-mediated endocytosis by blocking clathrin-coated pit formation. Two treatments, potassium depletion and hypertonic media, both inhibit endocytosis and lead to the formation of clathrin "microcages." These microcages appear as empty clathrin structures on the inner membrane surface and deplete the cytoplasm of clathrin needed for normal coated pit assembly. Hypertonic treatment causes coated pits to disappear and results in the formation of microcages, similar to potassium depletion. Both treatments lead to the loss of clathrin lattices and the dispersion of LDL receptors on the cell surface. However, upon return to normal conditions, these changes reverse, with clathrin lattices and receptor clusters reappearing. The formation of microcages is thought to be due to abnormal clathrin polymerization, possibly caused by cytoplasmic acidification. The study shows that both potassium depletion and hypertonic treatment lead to similar effects on clathrin and receptor distribution, suggesting that they inhibit endocytosis by rendering clathrin unavailable for normal coated pit assembly. The mechanisms underlying these effects are not fully understood, but the formation of microcages appears to be a key factor in the inhibition of endocytosis.