Changes in platelet free Ca2+ concentration after chronic digoxin treatment.
Cell Na+ and Ca2+ concentrations control each other by various mechanisms. In excitable cells from various origins, Ca2+ extrusion from the cell and its entry are dependent for a large part on the activity of the Na+, Ca2+-countertransport system. Cytosolic free Ca2+ concentration is also controlled by the Na+-H+ exchange activity. To analyze the changes in cytosolic Ca2+ concentration accompanying the reduction of the membrane Na+ gradient, cytosolic free Ca2+ concentration ([Ca2+]i) was measured by fluorescent dyes in platelets and erythrocytes from healthy subjects, before and during digoxin treatment (0.25 mg/day for 6 days). [Ca2+]i was increased in platelets from 169 +/- 30 to 321 +/- 61 nmol/l (n = 7, P less than 0.02) and unchanged in erythrocytes (121 +/- 6 and 104 +/- 7 nmol/l). This increase in platelet [Ca2+]i was not accompanied by a change in serotonin content (5.43 +/- 0.67 vs 5.49 +/- 0.61 10(-7) mol per 10(11) cells) and could not be reproduced by in vitro addition of 10(-4) mol/l ouabain (198 +/- 33 vs 186 +/- 73 nmol/l). The enhanced [Ca2+]i in platelets is thus not a short-term consequence of a reduced membrane Na+ gradient, but reflects either the overload of intracellular Ca2+ stores or an enhanced in vivo stimulation by hormones or neurotransmitters.
Le Quan-Sang
K H
KH
Département de Pharmacologie, U7 INSERM, Hôpital Necker, Paris, France.
David-Dufilho
M
M
Kerth
P
P
Pernollet
M G
MG
Frisk-Holmbert
M
M
Meyer
P
P
Devynck
M A
MA
D000328:Adult; D001792:Blood Platelets / Q000032:analysis* / Q000187:drug effects; D002118:Calcium / Q000097:blood*; D004077:Digoxin / Q000494:pharmacology*; D006801:Humans; D008297:Male; D008433:Mathematics; D010042:Ouabain / Q000494:pharmacology; D012964:Sodium / Q000097:blood
D010042:Ouabain; D004077:Digoxin; D012964:Sodium; D002118:Calcium