Transport pathways for lithium ions in neuroblastoma x glioma hybrid cells at 'therapeutic' concentrations of Li+.
The pathways of Li+ transport in neuroblastoma X glioma hybrid cells were studied at 2 mM external Li+. Five components of Li+ transport were identified. (1) A Na+-dependent Li+ countertransport system mediating Li+ transport in both directions across the plasma membrane. This transport pathway is insensitive to ouabain or external K+. It shows trans-stimulation (i.e. acceleration of Li+ extrusion by external Na+ and stimulation of Li+ uptake by internal Na+) and cis-inhibition (i.e. reduction of Li+ uptake by external Na+). (2) The Na+-K+ pump mediates Li+ uptake but not Li+ release in cells with physiological Na+ and K+ content. Li+ uptake by the pump in choline media is inhibited by both external Na+ and K+. In Na+ media, external K+ exhibits a biphasic effect: in concentrations up to about 1 mM, K+ accelerates, and at higher concentrations, K+ inhibits Li+ uptake by the pump. (3) Li+ can enter the voltage-dependent Na+ channel. Li+ uptake through this pathway is stimulated by veratridine and scorpion toxin, the stimulation being blocked by tetrodotoxin. Residual pathways comprise (4) a saturable component, which is comparable to basal Na+ uptake, and (5) a ouabain-resistant component promoting Li+ extrusion against an electrochemical gradient in choline media. The mechanisms for Li+ extrusion described here possibly explain how neuronal cells maintain the steady-state ratio of internal to external Li+ below 1 during chronic exposure to 1-2 mM external Li+.
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002460:Cell Line; D005910:Glioma / Q000378:metabolism*; D006822:Hybrid Cells / Q000378:metabolism*; D007700:Kinetics; D008094:Lithium / Q000378:metabolism* / Q000627:therapeutic use; D051379:Mice; D009447:Neuroblastoma / Q000378:metabolism*; D010042:Ouabain / Q000494:pharmacology; D011188:Potassium / Q000378:metabolism; D051381:Rats; D012604:Scorpion Venoms / Q000494:pharmacology; D012964:Sodium / Q000378:metabolism / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology; D014701:Veratridine / Q000494:pharmacology
D012604:Scorpion Venoms; D013779:Tetrodotoxin; D010042:Ouabain; D014701:Veratridine; D008094:Lithium; D012964:Sodium; D011188:Potassium