Evidence for an interaction between adducin and Na+-K+-ATPase: Relation to genetic hypertension

Mara Ferrandi, Sergio Salardi, Grazia Tripodi, Paolo Barassi, Rodolfo Rivera, Paolo Manunta, Rivka Goldshleger, Patrizia Ferrari, Giuseppe Bianchi, Steven J D Karlish

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Abstract

Adducin point mutations are associated with genetic hypertension in Milan hypertensive strain (MHS) rats and in humans. In transfected cells, adducin affects actin cytoskeleton organization and increases the Na+-K+- pump rate. The present study has investigated whether rat and human adducin polymorphisms differently modulate rat renal Na+-K+ATPase in vitro. We report the following. 1) Both rat and human adducins stimulate Na+-K+- ATPase activity, with apparent affinity in tens of nanomolar concentrations. 2) MHS and Milan normotensive strain (MNS) adducins raise the apparent ATP affinity for Na+-K+-ATPase. 3) The mechanism of action of adducin appears to involve a selective acceleration of the rate of the conformational change E2 (K)- E1 (Na) or E2(K). ATP → E1Na·ATP. 4) Apparent affinities for mutant rat and human adducins are significantly higher than those for wild types. 5) Recombinant human α- and β-adducins stimulate Na+-K+-ATPase activity, as do the COOH-terminal tails, and the mutant proteins display higher affinities than the wild types. 6) The cytoskeletal protein ankyrin, which is known to bind to Na+-K+-ATPase, also stimulates enzyme activity, whereas BSA is without effect; the effects of adducin and ankyrin when acting together are not additive. 7) Pig kidney medulla microsomes appear to contain endogenous adducin; in contrast with purified pig kidney Na+-K+ATPase, which does not contain adducin, added adducin stimulates the Na+-K+-ATPase activity of microsomes only about one-half as much as that of purified Na+- K+-ATPase. Our findings strongly imply the existence of a direct and specific interaction between adducin and Na+-K+-ATPase in vitro and also suggest the possibility of such an interaction in intact renal membranes.

Original languageEnglish
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume277
Issue number4 46-4
Publication statusPublished - Oct 1999

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Keywords

  • Blood pressure
  • Cytoskeleton
  • Genetics

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

Cite this

Ferrandi, M., Salardi, S., Tripodi, G., Barassi, P., Rivera, R., Manunta, P., Goldshleger, R., Ferrari, P., Bianchi, G., & Karlish, S. J. D. (1999). Evidence for an interaction between adducin and Na+-K+-ATPase: Relation to genetic hypertension. American Journal of Physiology - Heart and Circulatory Physiology, 277(4 46-4).