2009 - Inhibitory effect of Pb2+ on the transport cycle of the Na+,K+-ATPase

   SURFE²R ONE (a predecessor model of SURFE²R N1) publication in Chemical Research in Toxicology (2009)

Authors:
Gramigni E., Tadini-Buoninsegni F., Bartolommei G., Santini G., Chelazzi G., Moncelli M.R.

Journal:
Chemical Research in Toxicology (2009) 22(10):1699-1704

Abstract:

The effect of Pb²⁺ on the transport cycle of the Na⁺,K⁺-ATPase was characterized in detail at a molecular level by combining electrical and biochemical measurements. Electrical measurements were performed by adsorbing purified membrane fragments containing Na⁺,K⁺-ATPase on a solid-supported membrane. Upon adsorption, the Na⁺,K⁺-ATPase was activated by carrying out concentration jumps of different activating substrates, for example, Na⁺ and ATP. Charge movements following Na⁺,K⁺-ATPase activation were measured in the presence of various Pb²⁺ concentrations to investigate the effect of Pb²⁺ on different ion translocating steps of the pump cycle. These charge measurements were then compared to biochemical measurements of ATPase activity in the presence of increasing Pb2+ concentration. Our results indicate that Pb²⁺ inhibits cycling of the enzyme, but it does not affect cytoplasmic Na⁺ binding and release of Na⁺ ions at the extracellular side at concentrations below 10 μM. To explain the inhibitory effect of Pb²⁺ on the Na⁺,K⁺-ATPase, we propose that Pb²⁺ may interfere with the hydrolytic cleavage of the phosphorylated intermediate E₂P, which occurs in the K⁺-related branch of the pump cycle.

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