High intracellular Na+ preserves myocardial function at low heart rates in isolated myocardium from failing hearts.
We investigated the hypothesis that increased intracellular [Na+]i in heart failure contributes to preservation of SR Ca2+ load which may become particularly evident at slow heart rates. [Na+]i in SBFI-loaded myocytes from rabbits with pacing-induced heart failure (PHF) was significantly higher at each frequency as compared to Sham-operated animals. Furthermore, PHF rabbits demonstrated reduced SR Ca2+-ATPase protein levels (-37%, p < 0.04) but unchanged Na+/Ca2+ exchanger protein levels. At 0.25 Hz, isometric force was similar in cardiac trabeculae from PHF rabbits as compared to control (PHF, 3.6+/-1.3; Sham, 4.4+/-0.6 mN/mm2). Rapid cooling contractures (RCCs) were unchanged indicating preserved SR Ca2+ load at this frequency. In Sham, isometric twitch force increased with rising frequencies to 29.0+/-2.8 mN/mm2 at 3.0 Hz (p < 0.05) as compared to 0.25 Hz. RCCs showed a parallel increase by 186+/-47% (p < 0.01). In PHF, frequency-dependent increase in force (15.8+/-4.7 mN/mm2 at 3.0 Hz) and RCCs (increase by 70+/-40%) were significantly blunted. Thus, in PHF in rabbits SR Ca2+ load is preserved at low frequencies despite decreased SR Ca2+-ATPase expression. This may result from [Na+]i-dependent changes in Na+/Ca2+ exchanger activity.
Georg-August-Universität Göttingen, Herzzentrum, Kardiologie und Pneumologie, Robert-Koch-Str. 40, 37099 Göttingen, Germany. schiwolf@med.uni-goettingen.de
Wolfgang
W
Schillinger
Nils
N
Teucher
Claus
C
Christians
Michael
M
Kohlhaas
Samuel
S
Sossalla
Phuc
P
Van Nguyen
Albrecht G
AG
Schmidt
Ortwin
O
Schunck
Klaus
K
Nebendahl
Lars S
LS
Maier
Oliver
O
Zeitz
Gerd
G
Hasenfuss
D000818:Animals; D000252:Calcium-Transporting ATPases / Q000378:metabolism*; D004195:Disease Models, Animal; D004558:Electric Stimulation; D006333:Heart Failure / Q000378:metabolism*; D032342:Muscle Cells; D011817:Rabbits; D012519:Sarcoplasmic Reticulum / Q000378:metabolism; D012964:Sodium / Q000378:metabolism*; D019831:Sodium-Calcium Exchanger
D019831:Sodium-Calcium Exchanger; D012964:Sodium; D000252:Calcium-Transporting ATPases