Altered external pH transforms human erythrocytes from discocytes to s
tomatocytes (low pH) or echinocytes (high pH). The process is fast and
reversible at room temperature, so it seems to involve shifts in weak
inter- or intramolecular bonds. This shape change has been reported t
o depend on changes in membrane potential, but control experiments exc
luding roles for other simultaneously varying cell properties (cell pH
, cell water, and cell chloride concentration) were not reported. The
present study examined the effect of independent variation of membrane
potential on red cell shape. Red cells were equilibrated in a set of
solutions with graduated chloride concentrations, producing in them a
wide range of membrane potentials at normal cell pH and cell water. By
using assays that were rapid and accurate, cell pH, cell water, cell
chloride, and membrane potential were measured in each sample. Cells r
emained discoid over the entire range of membrane potentials examined
(-45 to +45 mV). It was concluded that membrane potential has no indep
endent effect on red cell shape and does not mediate the membrane curv
ature changes known to occur in red cells equilibrated at altered pH.