title: The modulation of pacing-induced changes in intracellular sodium levels by extracellular Ca2+ in isolated perfused rat hearts.
abstract: This study demonstrates the inverse relationship between extracellular free calcium ([Ca(o)]f) and intracellular sodium ([Na(i)]) in isolated perfused rat hearts and thus supports the role of [Na(i)] in the "calcium paradox". It also shows that the extent of the increase in [Na(i)] (delta[Na(i)]), and the extent of the decrease in left ventricular developed pressure (deltaLVDP) in isolated perfused rat hearts, induced by pacing, is modulated by [Ca(o)]f. At low (0.24 mM) as well as normal (1.15 mM) [Ca(o)]f, [Na(i)] increased with pacing, progressively and significantly (P<0.01 and P<0.05, respectively), reaching a maximum of 12.56 +/- 0.46 and 9.22 +/- 0.16 mM at 500 beats/min, respectively. At high [Ca(o)]f (2.2 mM), however, no pacing-induced increase in [Na(i)] was observed. Simultaneously, within the pacing range of 250-500 beats/min, the interval-force relationship was negative for all [Ca(o)]f. With decreasing [Ca(o)]f, a gradually increasing delta[Na(i)] was induced. We hypothesise that a [Ca(o)]f-dependent Na-Ca exchanger activity modulates Na+ uptake, and thus baseline [Na(i)]. During incremental pacing, the increase in pacing rate induces a [Ca(o)]f-dependent delta[Na(i)], which may interact further with the sarcolemmal Na-Ca exchanger activity. As a result, both baseline [Na(i)] and the pacing-induced, [Ca(o)]f-dependent delta[Na(i)] modulate the net Ca2+ uptake, and thus SR Ca, in a manner that results in a modulated left ventricular force development.
authors.affiliation: Department of Biochemistry & Molecular Genetics, University of Alabama at Birmingham, 35294-0006, USA.
authors.forename: T
authors.initials: T
authors.lastname: Simor
authors.forename: T
authors.initials: T
authors.lastname: Lóránd
authors.forename: B
authors.initials: B
authors.lastname: Gaszner
authors.forename: G A
authors.initials: GA
authors.lastname: Elgavish
mesh_terms: D000818:Animals; D002118:Calcium / Q000494:pharmacology*; D002304:Cardiac Pacing, Artificial; D006321:Heart / Q000187:drug effects / Q000502:physiology*; D066298:In Vitro Techniques; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D010477:Perfusion; D051381:Rats; D017207:Rats, Sprague-Dawley; D012964:Sodium / Q000378:metabolism*; D012975:Sodium Isotopes; D016277:Ventricular Function, Left; D017725:Ventricular Pressure
chemical_list: D012975:Sodium Isotopes; D012964:Sodium; D002118:Calcium