Ca2+-activated K+ efflux limits complement-mediated lysis of human erythrocytes.
The lytic effect of complement on human erythrocytes has been reported by others to increase when Na+ is substituted for K+ in the external medium. In this paper we have investigated the hypothesis that net loss of K+ through a K+ transport pathway protects erythrocytes from complement-induced colloidosmotic swelling and lysis. Antibody-sensitized human erythrocytes containing different intracellular cation concentrations (nystatin treatment) were exposed to low concentrations of guinea pig serum in media of different cation composition; complement lysis was assessed by the release of hemoglobin and the volume of the surviving cells estimated by their density distribution profiles. Complement-dependent swelling and lysis of erythrocytes (a) were limited by the presence of an outwardly directed K+ electrochemical gradient and (b) were enhanced by carbocyanine, a specific inhibitor of the Ca2+-activated K+ transport pathway, and by absence of Ca2+ in the external medium. We propose that during complement activation a rising cytosolic calcium triggers the Ca2+-activated K+ permeability pathway, the Gardos effect, produces a net K+, Cl- and water loss, and thus limits the colloidosmotic swelling and lysis of erythrocytes.
Halperin
J A
JA
Department of Cellular and Molecular Physiology, Harvard Medical School, Boston, Massachusetts 02115.
Brugnara
C
C
Nicholson-Weller
A
A
D000818:Animals; D001692:Biological Transport; D002118:Calcium / Q000502:physiology*; D002463:Cell Membrane Permeability; D003102:Colloids; D003167:Complement Activation; D004563:Electrochemistry; D004910:Erythrocyte Membrane / Q000502:physiology*; D006168:Guinea Pigs; D006461:Hemolysis; D006801:Humans; D007038:Hypotonic Solutions; D009997:Osmotic Pressure; D015221:Potassium Channels / Q000502:physiology*; D011189:Potassium Chloride; D012965:Sodium Chloride
D003102:Colloids; D007038:Hypotonic Solutions; D015221:Potassium Channels; D012965:Sodium Chloride; D011189:Potassium Chloride; D002118:Calcium