Molecular Pharmacology, Vol 10, 501-508, Copyright © 1974 by the American Society for Pharmacology and Experimental Therapeutics

Lithium and Rubidium Interactions with Sodium- and Potassium-Dependent Adenosine Triphosphatase: A Molecular Basis for the Pharmacological Actions of these Ions

¹ Department of Pharmacology, Michigan State University, East Lansing, Michigan 48824

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.

Note:
ACKNOWLEDGMENT The authors thank Mrs. Marilyn Turnbow for excellent technical assistance.

This article has been cited by other articles:

				T Akera Membrane adenosinetriphosphatase: a digitalis receptor? Science, November 11, 1977; 198(4317): 569 - 574. [Abstract] [PDF]