TY - JOUR T1 - Lithium and Rubidium Interactions with Sodium- and Potassium-Dependent Adenosine Triphosphatase: A Molecular Basis for the Pharmacological Actions of these Ions JF - Molecular Pharmacology JO - Mol Pharmacol SP - 501 LP - 508 VL - 10 IS - 3 AU - THOMAS TOBIN AU - TAI AKERA AU - C. S. HAN AU - THEODORE M. BRODY Y1 - 1974/05/01 UR - http://molpharm.aspetjournals.org/content/10/3/501.abstract N2 - Although lithium ion substitutes poorly for potassium ion in the reaction cycle of (Na+ + K+)-ATPase (ATP phosphohydrolase, EC 3.6.1.3), it consistently activated this enzyme in the presence of sodium and potassium. In contrast, rubidium ion, a much more effective substitute for potassium than lithium, was generally inhibitory in the presence of sodium and potassium. Li+ did not appear to activate the enzyme by stimulating its phosphorylation from ATP. Rather, Na+ was required for Li+ to stimulate ATPase activity, and Li+ directly (though weakly) stimulated dephosphorylation. Under conditions such that increasing concentrations of K+ and Rb+ inhibited turnover of the enzyme, Li+ stimulated its activity above values observed with K+ or Rb+. It appears that Li+ stimulates the turnover of the ATPase by triggering its dephosphorylation and dissociating rapidly from the dephospho-enzyme, thus allowing the enzyme to rephosphorylate readily. With Rb+ the stability of the dephospho-enzyme[unknown]rubidium complex hinders subsequent rephosphorylation of the enzyme and thus inhibits its turnover. Because Li+ and Rb+ respectively stimulate and inhibit (Na+ + K+)-ATPase relative to its activity in the presence of Na+ and K+, they may hyperpolarize or depolarize nerve cells in corresponding fashion. It is suggested that these actions of lithium and rubidium on the turnover of (Na+ + K+)-ATPase may be involved in their pharmacological actions. ACKNOWLEDGMENT The authors thank Mrs. Marilyn Turnbow for excellent technical assistance. ER -