Regulation of red blood cell filterability by Ca21 influx and cAMP-mediated signaling pathways

Oonishi, Tadahiro, Kanako Sakashita, and Nobuhiro Uyesaka. Regulation of red blood cell filterability by Ca21 influx and cAMP-mediated signaling pathways. Am. J. Physiol. 273 (Cell Physiol. 42): C1828–C1834, 1997.—To investigate the mechanism of the regulation of human red blood cell deformability, we examined the deformability under mechanical stress. Washed human red blood cells were rapidly injected through a fine needle, and their filterability was measured using a nickel mesh filter. The decrease in filterability showed a V-shaped curve depending on the extracellular Ca21 concentration; the maximum decrease was achieved at ,50 μM. The decreased filterability was accompanied by no change in cell morphology and cell volume, indicating that the decrease in filterability can be ascribed to alterations of the membrane properties. Ca21 entry blockers (nifedipine and felodipine) inhibited the impairment of filterability under mechanical stress. Prostaglandins E1 and E2, epinephrine, and pentoxifylline, which are thought to modulate the intracellular adenosine 38,58-cyclic monophosphate (cAMP) level of red blood cells, improved or worsened the impaired filterability according to their expected actions on the cAMP level of the cells. These results strongly suggest that the membrane properties regulating red blood cell deformability are affected by the signal transduction system, including Ca21-dependent and cAMP-mediated signaling pathways.