Cardiac basal metabolism: energetic cost of calcium withdrawal in the adult rat heart.
OBJECTIVE
Cardiac basal metabolism upon extracellular calcium removal and its relationship with intracellular sodium and calcium homeostasis was evaluated.


METHODS
A mechano-calorimetric technique was used that allowed the simultaneous and continuous measurement of both heat rate and resting pressure in arterially perfused quiescent adult rat hearts. Using pharmacological tools, the possible underlying mechanisms related to sodium and calcium movements were investigated.


RESULTS
Resting heat rate (expressed in mW g(-1)(dry wt)) increased upon calcium withdrawal (+4.4 +/- 0.2). This response was: (1) unaffected by the presence of tetrodotoxin (+4.3 +/- 0.6), (2) fully blocked by both, the decrease in extracellular sodium concentration and the increase in extracellular magnesium concentration, (3) partially blocked by the presence of either nifedipine (+2.8 +/- 0.4), KB-R7943 (KBR; +2.5 +/- 0.2), clonazepam (CLO; +3.1 +/- 0.3) or EGTA (+1.9 +/- 0.3). The steady heat rate under Ca(2+)-free conditions was partially reduced by the addition of Ru360 (-1.1 +/- 0.2) but not CLO in the presence of EGTA, KBR or Ru360.


CONCLUSIONS
Energy expenditure for resting state maintenance upon calcium withdrawal depends on the intracellular rise in both sodium and calcium. Our data are consistent with a mitochondrial Ca(2+) cycling, not detectable under normal calcium diastolic levels. The experimental condition here analysed, partially simulates findings reported under certain pathological situations including heart failure in which mildly increased levels of both diastolic sodium and calcium have also been found. Therefore, under such pathological conditions, hearts should distract chemical energy to fuel processes associated with sodium and calcium handling, making more expensive the maintenance of their functions.
Bonazzola
P
P
Instituto de Investigaciones Cardiológicas, Universidad de Buenos Aires-CONICET, Argentina. patri@biofis.odon.uba.ar <patri@biofis.odon.uba.ar>
Takara
D
D
D000818:Animals; D002118:Calcium / Q000172:deficiency* / Q000502:physiology*; D020013:Calcium Signaling / Q000502:physiology; D002352:Carrier Proteins / Q000378:metabolism; D002614:Chelating Agents / Q000494:pharmacology; D002998:Clonazepam / Q000494:pharmacology; D004533:Egtazic Acid / Q000494:pharmacology; D004734:Energy Metabolism / Q000502:physiology*; D018757:GABA Modulators / Q000494:pharmacology; D006321:Heart / Q000502:physiology*; D006339:Heart Rate / Q000187:drug effects; D006706:Homeostasis / Q000502:physiology; D066298:In Vitro Techniques; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D017975:Ruthenium Compounds / Q000494:pharmacology; D012964:Sodium / Q000378:metabolism; D019831:Sodium-Calcium Exchanger / Q000037:antagonists & inhibitors; D013779:Tetrodotoxin / Q000494:pharmacology; D022722:Thermogenesis / Q000502:physiology; D013890:Thiourea / Q000031:analogs & derivatives / Q000494:pharmacology
C101670:2-(2-(4-(4-nitrobenzyloxy)phenyl)ethyl)isothiourea methanesulfonate; D002352:Carrier Proteins; D002614:Chelating Agents; D018757:GABA Modulators; C112020:Ru 360; D017975:Ruthenium Compounds; D019831:Sodium-Calcium Exchanger; D013779:Tetrodotoxin; D004533:Egtazic Acid; D002998:Clonazepam; D012964:Sodium; D013890:Thiourea; D002118:Calcium