title: Na/Ca exchange and contraction of the heart.
abstract: Sodium-calcium exchange (NCX) is the major calcium (Ca) efflux mechanism of ventricular cardiomyocytes. Consequently the exchanger plays a critical role in the regulation of cellular Ca content and hence contractility. Reductions in Ca efflux by the exchanger, such as those produced by elevated intracellular sodium (Na) in response to cardiac glycosides, raise sarcoplasmic reticulum (SR) Ca stores. The result is an increased Ca transient and cardiac contractility. Enhanced Ca efflux activity by the exchanger, for example during heart failure, may reduce diadic cleft Ca and excitation-contraction (EC) coupling gain. This aggravates the impaired contractility associated with SR Ca ATPase dysfunction and reduced SR Ca load in failing heart muscle. Recent data from our laboratories indicate that NCX can also impact the efficiency of EC coupling and contractility independent of SR Ca load through diadic cleft priming with Ca during the upstroke of the action potential. This article is part of a Special Issue entitled "Na(+) Regulation in Cardiac Myocytes".
authors.affiliation: Heart Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
authors.forename: Michela
authors.initials: M
authors.lastname: Ottolia
authors.forename: Natalia
authors.initials: N
authors.lastname: Torres
authors.forename: John H B
authors.initials: JH
authors.lastname: Bridge
authors.forename: Kenneth D
authors.initials: KD
authors.lastname: Philipson
authors.forename: Joshua I
authors.initials: JI
authors.lastname: Goldhaber
mesh_terms: D000200:Action Potentials; D000818:Animals; D001692:Biological Transport; D002118:Calcium / Q000378:metabolism*; D021961:Cell Membrane Structures / Q000378:metabolism; D056966:Excitation Contraction Coupling; D006333:Heart Failure / Q000378:metabolism / Q000503:physiopathology; D006801:Humans; D009200:Myocardial Contraction; D012519:Sarcoplasmic Reticulum / Q000378:metabolism; D012964:Sodium / Q000378:metabolism*; D019831:Sodium-Calcium Exchanger / Q000378:metabolism
chemical_list: D019831:Sodium-Calcium Exchanger; D012964:Sodium; D002118:Calcium
keywords: AP; Ca; Calcium; EC; Excitation contraction coupling; Genetically modified mice; Heart contractility; Heart failure; KO; L-type Ca channels; LCCs; NCX; NCX knockout mouse; RyRs; SR; Sodium calcium exchanger; action potential; calcium; excitation–contraction coupling; ryanodine receptor; sarcoplasmic reticulum; sodium calcium exchanger