Effects of high external concentrations of K+ on 86Rb+ efflux in human platelets: evidence for Na+/K+/2Cl- co-transport.
1. Na+/K+/2Cl- co-transport mediates a bidirectional symport of Na+, K+ and Cl-. The important properties of the co-transport system are its requirement for Na+, K+ and Cl- and its inhibition by loop diuretics such as bumetanide. This co-transporter has been described in a number of animal and human tissues. However, its presence in human platelets, although inferred, has not been demonstrated directly. 2. We have studied the efflux of 86Rb+ (a marker for K+) from Rb(+)-loaded platelets, and have defined their response to stimulation by high concentrations of external K+. 3. KCl (30-120 mmol/l) stimulated a concentration-dependent increase in 86Rb+ efflux from the platelets. This efflux was completely inhibited by bumetanide (10 mumol/l) but was insensitive to ouabain and R(+)-[(dihydroindenyl)oxy]alkanoic acid. It also required Cl- in the external medium, but did not depend on the presence of extracellular Na+. 4. These observations suggest that 86Rb+ efflux from platelets stimulated by external K+ occurs via Na+/K+/2Cl- co-transport acting in a K+/K+ (K+/Rb+) exchange mode. 5. Non-stimulated efflux of 86Rb+ from the platelets (i.e. in the presence of 5 mmol/l K+) had the characteristics of Na+/K+/2Cl- co-transport acting in normal mode.
de Silva
H A
HA
University Department of Clinical Pharmacology, Radcliffe Infirmary, Oxford, UK.
Carver
J G
JG
Aronson
J K
JK
D000328:Adult; D001692:Biological Transport / Q000187:drug effects; D001792:Blood Platelets / Q000378:metabolism*; D002034:Bumetanide / Q000494:pharmacology; D002264:Carboxylic Acids / Q000494:pharmacology; D018929:Cell Culture Techniques; D002713:Chlorine / Q000097:blood*; D006801:Humans; D007192:Indenes / Q000494:pharmacology; D010042:Ouabain / Q000494:pharmacology; D011188:Potassium / Q000097:blood*; D012414:Rubidium Radioisotopes / Q000097:blood; D012964:Sodium / Q000097:blood*
C059990:((dihydroindenyl)oxy)alkanoic acid; D002264:Carboxylic Acids; D007192:Indenes; D012414:Rubidium Radioisotopes; D002034:Bumetanide; D002713:Chlorine; D010042:Ouabain; D012964:Sodium; D011188:Potassium