A hypothesis on the role of the electrical charge of haemoglobin in regulating the erythrocyte shape

Abstract

A previously proposed mechanism of erythrocyte shape has been proposed in which the ratio of the two conformations of Band 3, the anion exchange protein, controls the erythrocyte shape by modifying the degree of contraction or relaxation of the membrane skeleton. This mechanism was previously shown to explain several observations related and unrelated to the erythrocyte shape. We show that it can also explain the occurrence of target cells in blood smears of individuals expressing Hb A variants with significantly lower and higher isoelectric points. This would provide further support of its validity and would have the following implications. The electrical charge of of Hb A influences the erythrocyte shape and deformability, thus explaining the low level of expression of Hb A2 with an isoelectric point significantly higher than Hb A. It would suggest that Hb A2 has a physiological function related to the control of the erythrocyte shape. This could be of regulating the activity of the K–Cl cotransport system or of tuning finely the cell pH. A role of haemoglobin in the control of the erythrocyte shape would ensure a more efficient oxygenation of tissues and removal of carbon dioxide generated by tissues. It would also provide a basis for the absence of spreading in populations of some haemoglobin variants differing only by the electrical charge.