Functional significance of the intermediate conductance Ca2+-activated K+ channel for the short-term survival of injured erythrocytes. Academic Article uri icon

abstract

  • Increased cytosolic Ca(2+) concentrations activate Gardos K(+) channels in human erythrocytes with membrane hyperpolarization, efflux of K(+), Cl, and osmotically obliged HO resulting in cell shrinkage, a phenomenon referred to as Gardos effect. We tested whether the Gardos effect delays colloid osmotic hemolysis of injured erythrocytes from mice lacking the Ca(2+)-activated K(+) channel K(Ca)3.1. To this end, we applied patch clamp and flow cytometry and determined in vitro as well as in vivo hemolysis. As a result, erythrocytes from K(Ca)3.1-deficient (K(Ca)3.1(-/-)) mice lacked Gardos channel activity and the Gardos effect. Blood parameters, reticulocyte count, or osmotic erythrocyte resistance, however, did not differ between K(Ca)3.1(-/-) mice and their wild-type littermates, suggesting low or absent Gardos channel activity in unstressed erythrocytes. Oxidative stress-induced Ca(2+) entry and phospholipid scrambling were significantly less pronounced in K(Ca)3.1(-/-) than in wild-type erythrocytes. Moreover, in vitro treatment with -toxin from Staphylococcus aureus, which forms pores in the cellular membrane, resulted in significantly stronger hemolysis of K(Ca)3.1(-/-) than of wild-type erythrocytes. Intravenous injection of -toxin induced more profound hemolysis in K(Ca)3.1(-/-) than in wild-type mice. Similarly, intra-peritoneal application of the redox-active substance phenylhydrazine, an agent for the induction of hemolytic anemia, was followed by a significantly stronger decrease of hematocrit in K(Ca)3.1(-/-) than in wild-type mice. Finally, malaria infection triggered the activation of K(Ca)3.1 and transient shrinkage of the infected erythrocytes. In conclusion, K(Ca)3.1 channel activity and Gardos effect counteract hemolysis of injured erythrocytes, thus decreasing hemoglobin release into circulating blood.

published proceedings

  • Pflugers Arch

altmetric score

  • 3

author list (cited authors)

  • Fller, M., Bobbala, D., Koka, S., Boini, K. M., Mahmud, H., Kasinathan, R. S., ... Huber, S. M.

citation count

  • 19

complete list of authors

  • Föller, Michael||Bobbala, Diwakar||Koka, Saisudha||Boini, Krishna M||Mahmud, Hasan||Kasinathan, Ravi S||Shumilina, Ekaterina||Amann, Kerstin||Beranek, Golo||Sausbier, Ulrike||Ruth, Peter||Sausbier, Matthias||Lang, Florian||Huber, Stephan M

publication date

  • November 2010