title: Manipulation of intracellular sodium by extracellular divalent cations: a 23Na and 31P NMR study on intact rat hearts.
abstract: 23Na and 31P NMR spectroscopy were used to follow intracellular [Na+] ([Na+]i) and energy metabolism in isolated, perfused rat hearts. During 30 min of Ca(2+)-free perfusion no significant change in [Na+]i could be detected, but during a subsequent 45 min period of ischemia [Na+]i rose significantly as expected, from 8.6 +/- 2.4 to 36.8 +/- 9.4 mM. In contrast, already during 30 min of Ca(2+)- and Mg(2+)-free perfusion [Na+]i rose significantly from 7.3 +/- 3.7 to 71.3 +/- 15.6 mM. During this period, the Na(+)-K+ ATPase was not limited by depletion of high energy phosphates, decrease of intracellular free Mg2+ or accumulation of inorganic phosphate. During the first 8 min of a subsequent period of ischemia, the rate of rise in [Na+]i even increased, suggesting that during the preceding period of Ca(2+)- and Mg(2+)-free perfusion, the Na(+)-K+ ATPase was indeed operative but apparently not coping with the large Na(+)-influx. Using verapamil, we could demonstrate that this large Na(+)-influx occurs through the L-type Ca2+ channels, and that both Mg2+ and verapamil can block this Na(+)-influx. Previously, we have demonstrated that [Na+]i does not play a role in the origin of the calcium paradox. The notion that an increased [Na+]i is a prerequisite for the calcium paradox to occur apparently results from experimental evidence obtained under conditions of low or absent Mg2+.
authors.affiliation: Department of Cardiology, University Hospital, Utrecht, The Netherlands.
authors.forename: C J
authors.initials: CJ
authors.lastname: Van Echteld
authors.forename: J G
authors.initials: JG
authors.lastname: Van Emous
authors.forename: M A
authors.initials: MA
authors.lastname: Jansen
authors.forename: J H
authors.initials: JH
authors.lastname: Schreur
authors.forename: T J
authors.initials: TJ
authors.lastname: Ruigrok
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000494:pharmacology / Q000502:physiology*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002122:Calcium Chloride / Q000494:pharmacology; D002413:Cations, Divalent; D066298:In Vitro Techniques; D008274:Magnesium / Q000378:metabolism* / Q000494:pharmacology; D015636:Magnesium Chloride / Q000494:pharmacology; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D008297:Male; D017202:Myocardial Ischemia; D009206:Myocardium / Q000378:metabolism*; D010477:Perfusion; D010725:Phosphocreatine / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012964:Sodium / Q000378:metabolism*; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D014700:Verapamil / Q000494:pharmacology
chemical_list: D002121:Calcium Channel Blockers; D002413:Cations, Divalent; D010725:Phosphocreatine; D015636:Magnesium Chloride; D000255:Adenosine Triphosphate; D012964:Sodium; D014700:Verapamil; D000254:Sodium-Potassium-Exchanging ATPase; D008274:Magnesium; D002122:Calcium Chloride; D002118:Calcium