The role of calmodulin on Ca2+ -dependent K+ transport regulation in the human red cell.
Several lipophilic calmodulin antagonists (phenotiazines, butyrophenones and diphenylbutylpiperidines) inhibited Ca2+-induced loss of KC1 from human red cells. However, the Ki values for this effect did not bear good correlation with the Ki values reported for well-known calmodulin-dependent systems. In addition, the inhibition was strongly dependent on the haematocrit and valinomycin-induced KC1 fluxes were also affected. Added calmodulin did not have any effect on Ca2+-dependent 86Rb uptake by inside-out vesicles derived from red cell membranes whereas stimulation of Ca2+-dependent ATPase was apparent. Lipophilic anticalmodulins at high doses had all kinds of effects on 86Rb uptake by inside-out vesicles: increase, decrease or no change of the fraction of activated vesicles reached at submaximal Ca2+ concentrations, with or without modification of the relative rate of 86Rb uptake. The hydrophylic compound 48/80 decreased the fraction of activated vesicles reached at submaximal Ca2+ concentrations without affecting the relative rate of 86Rb uptake, but this effect took place only at concentrations 10-fold higher than the reported Ki for calmodulin-dependent systems. These results suggest that Ca2+-dependent K+ channels of red cells are not regulated by calmodulin.
D001692:Biological Transport / Q000187:drug effects; D002090:Butyrophenones / Q000494:pharmacology; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000097:blood; D000252:Calcium-Transporting ATPases / Q000097:blood; D002147:Calmodulin / Q000037:antagonists & inhibitors / Q000097:blood*; D004910:Erythrocyte Membrane / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D010640:Phenothiazines / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D011188:Potassium / Q000097:blood*; D012413:Rubidium / Q000378:metabolism; D014634:Valinomycin / Q000494:pharmacology; D003189:p-Methoxy-N-methylphenethylamine / Q000494:pharmacology
D002090:Butyrophenones; D002147:Calmodulin; D010640:Phenothiazines; D010880:Piperidines; D014634:Valinomycin; D000001:Calcimycin; D003189:p-Methoxy-N-methylphenethylamine; D000252:Calcium-Transporting ATPases; C031637:phenothiazine; D012413:Rubidium; D011188:Potassium; D002118:Calcium