Talk abstract:

A Working Mechanism of the Sodium Pump

Bruce A. Benjamin
Oklahoma State University
College of Osteopathic Medicine
Tulsa, OK 74107
benjamb@osu-com.okstate.edu

Joint work with E. A. Johnson, El Laboratorio de Fisiologia Cuantitativo, 04638 Mojacar Almeria, Spain.

Computer simulation of the classical Post-Albers scheme for the reaction cycle of the sodium pump (characterized by single translocational steps (E₁ leftrightarow E₂) for N_a+ & K⁺) gave a poor fit to the non-vectorial activation of the enzyme by Na⁺ & K⁺ and the binding of K⁺ to the Na⁺-free enzyme. However, the inclusion of an intermediate ("occluded") translocational state for both Na⁺ & K⁺ abolished this limitation. The resulting best, simultaneous, fits to the Na⁺ & K⁺ activation and K⁺-binding data showed that the optimized rate constants for the additional steps for translocation of Na⁺ and the MgATP-free-K⁺-bound forms of the enzyme assumed values consistent with these steps being "de-occlusion" steps. The equilibrium constants of these steps were of the order Of 10^-6 and the on-rate for binding of the ions to the E₂ form of the enzyme approached 10¹⁰ M^-1 sec^-1 -the on-rate for binding of small ions (free of H₂O). The second translocational step for the K⁺-MgATP-bound form of the enzyme effectively disappeared in that the forward and reverse rates of the step became equally large, as though the regulatory effect of MgATP binding to the E₂ form was to effectively remove the "occluded" state. In addition, with minor changes in parameter values, this enhanced Post-Albers scheme gave excellent fits to vectorial pump activity in single, isolated cardiac muscle cells. Such fits included the activation of membrane pump-generated current by intracellular [Na⁺], extracellular [K⁺], and the relationship between pump current and transmembrane potential at various extracellular [Na⁺]. Given this working mechanism for the sodium pump and the corresponding mechanism for the Na,K,2Cl cotransporter (Benjamin, B.A. & E.A. Johnson, Am. J. Physiol., 273: 473-482, 1997), it will now be possible to study their cooperative role in the regulation of intracellular Na⁺, K⁺ and C1^-.

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1998-1999 Mathematics in Biology