Proposed model for the formation of ID and HD cells from young ND SS red blood cells by two independent pathways. Pathway I primarily mediates formation of ID cells and its properties are consistent with K:Cl cotransport. HbS polymerization plays a smaller role in dense cells formed by this pathway. Pathway II primarily mediates formation of HD cells and its properties are consistent with the K(Ca2+) channel. HbS polymerization plays a larger role in dense cells formed by this pathway. ND, ID, and HD cells are defined in Fig 1. O-D, O-D cycling; deoxygenation, continuous deoxygenation with 5% CO2/balance N2; Cl−-dependency was determined as the activity remaining after substitution of Cl− with NO3−; ATP depletion was accomplished by substitution of 2-deoxyglucose for glucose; OKA, DIOA, CTX, and CLT are defined in Fig 6.
