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Title: Monensin-induced reversal of positive force-frequency relationship in cardiac muscle: role of intracellular sodium in rest-dependent potentiation of contraction
Authors: Mubagwa, Kanigula ×
Lin, Wei
Sipido, Karin
Bosteels, Suzanne
Flameng, Willem #
Issue Date: Mar-1997
Series Title: Journal of Molecular and Cellular Cardiology vol:29 issue:3 pages:977-89
Abstract: We have investigated the role of a rest-dependent inotropic factor in determining species-related differences in cardiac force-frequency relationships (FFR). Isolated rat, rabbit or guinea-pig papillary muscles, as well as guinea-pig ventricular myocytes were superfused with 1.8 mM Ca2+ Tyrode. In rat muscles, isometric force amplitude decreased, while in rabbit or guinea-pig muscles force increased with frequency (0.02-1 Hz). Paired-pulse pacing potentiated contraction markedly at all frequencies in rabbit muscles, but not at low frequencies in rat muscles. We tested the hypothesis that high intracellular Na+ levels (Nai) are responsible for negative FFR. The ionophore monensin increased Nai, reversed the FFR of rabbit and guinea-pig muscles from positive to negative, by increasing force mostly at low frequencies, and decreased the paired-pulse potentiation of contraction at low frequencies. Monensin added during rest also reversed rest-induced decay. In isolated myocytes, monensin had qualitatively similar effects on cell shortening as well as on Cai transients. Monensin also decreased the action potential duration (APD) but did not change the pattern of its variation with frequency. Cells intracellularly dialyzed with 20 mM Na+ via a patch pipette also showed rest potentiation of the Cai transients, in contrast to cells dialyzed with 10 mM Na+, which showed rest decay of the transients. APD was also shorter in myocytes dialyzed with 20 mM Na+ than in those dialyzed with lower Na+. The results indicate that in the presence of high Nai, sarcoplasmic reticular Ca2+ load is increased during diastole, possibly via reverse-mode Na+/Ca2+ exchange, and therefore that Nai is an important factor determining the FFR. In addition, the data suggest that short APDs in preparations showing negative FFR may be partly a consequence of increased Nai.
URI: 
ISSN: 0022-2828
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Experimental Cardiac Surgery
Cardiology
Physiology Section (-)
Experimental Cardiology
× corresponding author
# (joint) last author

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