title: Intracellular Na(+) concentration is elevated in heart failure but Na/K pump function is unchanged.
abstract: BACKGROUND
  Intracellular sodium concentration ([Na(+)](i)) modulates cardiac contractile and electrical activity through Na/Ca exchange (NCX). Upregulation of NCX in heart failure (HF) may magnify the functional impact of altered [Na(+)](i).
  
  
  RESULTS
  We measured [Na(+)](i) by using sodium binding benzofuran isophthalate in control and HF rabbit ventricular myocytes (HF induced by aortic insufficiency and constriction). Resting [Na(+)](i) was 9.7+/-0.7 versus 6.6+/-0.5 mmol/L in HF versus control. In both cases, [Na(+)](i) increased by approximately 2 mmol/L when myocytes were stimulated (0.5 to 3 Hz). To identify the mechanisms responsible for [Na(+)](i) elevation in HF, we measured the [Na(+)](i) dependence of Na/K pump-mediated Na(+) extrusion. There was no difference in V(max) (8.3+/-0.7 versus 8.0+/-0.8 mmol/L/min) or K(m) (9.2+/-1.0 versus 9.9+/-0.8 mmol/L in HF and control, respectively). Therefore, at measured [Na(+)](i) levels, the Na/K pump rate is actually higher in HF. However, resting Na(+) influx was twice as high in HF versus control (2.3+/-0.3 versus 1.1+/-0.2 mmol/L/min), primarily the result of a tetrodotoxin-sensitive pathway.
  
  
  CONCLUSIONS
  Myocyte [Na(+)](i) is elevated in HF as a result of higher diastolic Na(+) influx (with unaltered Na/K-ATPase characteristics). In HF, the combined increased [Na(+)](i), decreased Ca(2+) transient, and prolonged action potential all profoundly affect cellular Ca(2+) regulation, promoting greater Ca(2+) influx through NCX during action potentials. Notably, the elevated [Na(+)](i) may be critical in limiting the contractile dysfunction observed in HF.
authors.affiliation: Department of Physiology, Loyola University Chicago, Maywood, IL 60153, USA.
authors.forename: Sanda
authors.initials: S
authors.lastname: Despa
authors.forename: Mohammed A
authors.initials: MA
authors.lastname: Islam
authors.forename: Christopher R
authors.initials: CR
authors.lastname: Weber
authors.forename: Steven M
authors.initials: SM
authors.lastname: Pogwizd
authors.forename: Donald M
authors.initials: DM
authors.lastname: Bers
mesh_terms: D000200:Action Potentials; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002469:Cell Separation; D003971:Diastole; D004195:Disease Models, Animal; D004558:Electric Stimulation; D006333:Heart Failure / Q000473:pathology / Q000503:physiopathology*; D066298:In Vitro Techniques; D007424:Intracellular Fluid / Q000378:metabolism*; D008564:Membrane Potentials; D009200:Myocardial Contraction; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D009532:Nickel / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D011817:Rabbits; D012964:Sodium / Q000378:metabolism*; D026941:Sodium Channel Blockers; D015222:Sodium Channels / Q000378:metabolism; D019831:Sodium-Calcium Exchanger / Q000037:antagonists & inhibitors / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000187:drug effects / Q000378:metabolism*; D013327:Strophanthidin / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology
chemical_list: D026941:Sodium Channel Blockers; D015222:Sodium Channels; D019831:Sodium-Calcium Exchanger; D013779:Tetrodotoxin; D013327:Strophanthidin; D009532:Nickel; D012964:Sodium; D000254:Sodium-Potassium-Exchanging ATPase; D002118:Calcium