title: A calmodulin activated Ca2+-dependent K+ channel in human erythrocyte membrane inside-out vesicles.
abstract: The role of calmodulin in stimulating active calcium transport in the human red cell membrane is well documented. In contrast, efforts to characterize the effect of calmodulin on the Ca2+-dependent K+ channel in erythrocyte membranes have given rise to conflicting reports. These studies have indicated that experimental conditions may play a critical role in preserving the Ca2+-dependent K+ channels in erythrocyte inside-out vesicles. With these observations in mind, a double-labelling study of simultaneous active Ca2+ and passive Rb+ uptake in red-cell inside-out vesicles was undertaken. Addition of calmodulin and ATP to a suspension of inside-out vesicles containing 1 mM K+ caused a Ca2+-dependent increase in both the rate of active calcium transport and Rb+ uptake. The initial Rb+ isotope flux was increased 3-fold over the rate observed in the absence of calmodulin. The k1/2 for activation of K+ permeability was approx. 5 X 10(-7) M Ca2+ as compared to 10(-6) M Ca2+ for active Ca2+ transport. Addition of the calmodulin antagonists pimozide and chlorpromazine blocked calmodulin activation of the Ca2+-dependent K+ channel. The observation that activation of the K+ channel occurs at Ca2+ concentrations which are lower than those required for maximum stimulation of the calcium pump suggests that these processes are dependent on two states of the calmodulin molecule, characterized by a lower or higher amount of Ca2+ bound to calmodulin.
mesh_terms: D000255:Adenosine Triphosphate / Q000097:blood; D002118:Calcium / Q000097:blood*; D002147:Calmodulin / Q000494:pharmacology*; D002746:Chlorpromazine / Q000494:pharmacology; D004910:Erythrocyte Membrane / Q000378:metabolism*; D006801:Humans; D007473:Ion Channels / Q000378:metabolism*; D007700:Kinetics; D010868:Pimozide / Q000494:pharmacology; D011188:Potassium / Q000097:blood*; D012413:Rubidium / Q000097:blood
chemical_list: D002147:Calmodulin; D007473:Ion Channels; D010868:Pimozide; D000255:Adenosine Triphosphate; D012413:Rubidium; D011188:Potassium; D002118:Calcium; D002746:Chlorpromazine