Calcium-activated sodium and chloride fluxes modulate platelet volume: role of Ca2+ stores.
An increase in cytosolic ionized Ca2+ concentration ([Ca2+]i) initiates volume changes in various types of cells. In response to increases in [Ca2+]i most cell types contract by efflux of K+ and Cl-, whereas platelets expand in response to rises in [Ca2+]i. This study examined the importance of the source of Ca2+, the flux of ions responsible for the volume change, and the role of Ca(2+)-dependent protein kinases in regulating these ionic fluxes. The baseline platelet volume was independent of extracellular Ca2+ but when stimulated by the Ca2+ ionophore A-23187 (50 nM) the volume increased in both the presence and absence of extracellular Ca2+ (1.18 +/- 0.08 vs. 0.83 +/- 0.06 fl, respectively). The increased volume was caused by the gain of Na+ and Cl-. Na+ entered through both conductive and nonconductive (Na+/H+ exchange) pathways, whereas the influx of Cl- was conductive and inhibited by the Cl- channel blocker 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid. The Ca(2+)-induced volume change was blocked by both calmodulin and protein kinase inhibitors. Thus the activation of Ca(2+)-dependent protein kinases promotes platelet swelling by stimulating Na+ and Cl- influx.
Department of Pediatrics, New Jersey Medical School, University of Medicine and Dentistry of New Jersey, Newark 07103.
B P
BP
Fine
E S
ES
Marques
K A
KA
Hansen
D001792:Blood Platelets / Q000166:cytology* / Q000378:metabolism*; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology* / Q000502:physiology*; D002147:Calmodulin / Q000502:physiology; D002712:Chlorides / Q000378:metabolism*; D006801:Humans; D007425:Intracellular Membranes / Q000378:metabolism; D009994:Osmolar Concentration; D011494:Protein Kinases / Q000502:physiology; D012964:Sodium / Q000378:metabolism*; D017871:Calcium-Calmodulin-Dependent Protein Kinases
D000001:Calcimycin; D002118:Calcium; D002147:Calmodulin; D002712:Chlorides; D011494:Protein Kinases; D012964:Sodium; D017871:Calcium-Calmodulin-Dependent Protein Kinases