Distinction of two components of passive Ca2+ transport into human erythrocytes by Ca2+ entry blockers.
The nature of downhill Ca2+ net-transport into human erythrocytes was investigated using the experimental models of Ca2+ pump inhibition by vanadate and of intracellular chelation of Ca2+ by quin2. Ca2+ uptake by erythrocytes loaded with 0.5 mM vanadate and suspended in 145 mM Na+ -5 mM K+ media was reduced by about 60% when medium K+ was raised to 80 mM. Organic and inorganic Ca2+ entry blockers such as nifedipine (10(-5) M), verapamil (10(-4) M), diltiazem (10(-4) M), Co2+ (1.5 mM) and Cu2+ (0.1 mM) as well as the K+ channel blocker quinidine (1mM) inhibited Ca2+ uptake in 145 mM Na+ -5 mM K+ media by 60-75%. Flunarizine was less effective. In vanadate-loaded cells suspended in 70 mM Na+ -80 mM K+ media, in contrast, flunarizine exerted a dose-dependent inhibition of Ca2+ uptake by up to 80% at 10(-5) M, the other blockers being ineffective (except for verapamil at 10(-4) M). A similar pattern of inhibition was seen in quin2-loaded erythrocytes. The different susceptibility towards inhibitors may indicate that passive Ca2+ uptake by vanadate-loaded erythrocytes suspended in 145 mM Na+ -5 mM K+ media, on the one hand, and by vanadate-loaded erythrocytes suspended in 70 mM Na+ -80 mM K+ media as well as by quin2-loaded erythrocytes, on the other hand, is mediated by two different transport components.
Engelmann
B
B
Department of Physiology, University of Munich, F.R.G.
Duhm
J
J
D000634:Aminoquinolines / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism*; D002463:Cell Membrane Permeability / Q000187:drug effects*; D003035:Cobalt / Q000494:pharmacology; D003300:Copper / Q000494:pharmacology; D004110:Diltiazem / Q000494:pharmacology; D004910:Erythrocyte Membrane / Q000187:drug effects / Q000378:metabolism*; D005444:Flunarizine / Q000494:pharmacology; D006801:Humans; D009543:Nifedipine / Q000494:pharmacology; D014638:Vanadates / Q000494:pharmacology; D014700:Verapamil / Q000494:pharmacology
D000634:Aminoquinolines; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D003035:Cobalt; D014638:Vanadates; D003300:Copper; D014700:Verapamil; D004110:Diltiazem; D009543:Nifedipine; C035739:Quin2; D005444:Flunarizine; D002118:Calcium