Related Experiment Video
Updated: Aug 6, 2026
Electrocardiogram Recordings in Anesthetized Mice using Lead II
Published on: June 20, 2020
Lithium and KB-R7943 effects on mechanics and energetics of rat heart muscle
P Bonazzola1, P Egido, F D Marengo
1Instituto de Investigaciones Cardiológicas, Facultad de Medicina, Universidad de Buenos Aires - CONICET and Cátedra de Biofísica, Facultad de Odontología - UBA, Buenos Aires, Argentina.
Insights
This study investigated how calcium influx affects cardiac contraction energy. Lithium and KB-R 7943 (KBR) were used to block calcium entry via the sodium-calcium exchanger, revealing insights into cardiac energy expenditure during contraction.
Area of Science:
- Cardiology
- Biophysics
- Cell Physiology
Background:
- Cardiac contraction relies on calcium (Ca) influx, influencing energy expenditure.
- The sodium-calcium exchanger (NCX) plays a role in regulating intracellular Ca levels.
- Understanding Ca influx mechanisms is crucial for cardiac energy metabolism research.
Purpose of the Study:
- To investigate the role of calcium influx in cardiac contraction energy expenditure.
- To examine the effects of inhibiting the sodium-calcium exchanger on cardiac mechanical function and energy release.
- To explore potential additional targets of lithium beyond the NCX in cardiac cells.
Main Methods:
- Utilized isolated cardiac muscle preparations.
- Administered lithium chloride (LiCl) and KB-R 7943 (KBR) to inhibit calcium entry via the sodium-calcium exchanger.
- Measured developed pressure, pressure-time integral, and heat production components (H1-H4) during various contraction protocols, including isolated, regular, and extra-systole (ES) contractions.
Main Results:
- Lithium and KBR significantly reduced pressure and energy release during ES contractions, primarily by inhibiting Ca entry via the NCX.
- Both agents decreased the H2 energy component associated with Ca cycling.
- Lithium also reduced the H4 component related to mitochondrial processes in isolated contractions, enhancing overall economy.
- Combined Li and KBR treatment abolished ES in 77% of cases, suggesting additive effects.
Conclusions:
- Inhibition of calcium influx via the sodium-calcium exchanger reduces cardiac energy expenditure during contractions, particularly those dependent on extracellular calcium.
- Lithium may have additional effects on calcium-sensitive targets in the heart, influencing mitochondrial energy release.
- These findings support the role of NCX in cardiac Ca influx and offer insights into the mechanisms of cardiac energy metabolism.
Abstract:
The role of calcium influx on energy expenditure during cardiac contraction was studied. For this purpose, the described ability of lithium and KB-R 7943 (KBR) to diminish Ca entry through Na-Ca exchanger (Ponce-Hornos & Langer, J Mol Cell Cardiol 1980, 12, 1367, Satoh et al., Circulation 2000, 101, 1441) were used. In isolated contractions (contractions elicited after at least 5 min of rest) LiCl 45 mmol L(-1) decreased pressure developed and pressure-time integral from 42.3 +/- 2.7 and 14.5 +/- 1.2 to 32.1 +/- 3.4 mN mm(-2) and 8.3 +/- 0.9 mN mm(-2) s, respectively. A similar effect was observed in regular contractions (at 0.16 Hz stimulation). The presence of KBR (5 micromol L(-1)) in the perfusate induced a slight but not significant decrease in pressure developed and pressure-time integral in steady-state contractions. As it was previously described, the heat involved in a heart muscle contraction can be decomposed into several components (H1, H2, H3 and H4), but only one (H3) was associated with force generation. While H3 decreased with lithium in both types of contractions, H3/PtI ratio remained unaltered, indicating that the economy for pressure maintenance was unaffected. To further investigate the role of Ca entry on force development, a condition in which the contraction is mainly dependent on extracellular calcium was studied. An 'extra' stimulus applied 200 ms after the regular one in a muscle stimulated at 0.16 Hz induces a contraction with this characteristic (Marengo et al., Am J Physiol 1999, 276, H309). Lithium induced a strong decrease in pressure-time integral and H3 associated with this contraction (43 and 45%, respectively) with no change in H3/PtI ratio. Lithium also reduced (53%) an energy component (H2) associated with Ca cycling. The use of KBR showed qualitatively similar results [i.e. a 33% reduction in pressure-time integral associated with the extrasystole (ES) with no changes in H3/PtI ratio and a 30% reduction in the H2 component]. Li and KBR effects appear to be additive and in the presence of 45 mmol L(-1) Li and 5 micromol L(-1) KBR the extrasystole was abolished in 77%. Lithium and KBR effects particularly for the extrasystole can be explained through the inhibition of Ca entry via Na-Ca exchange giving support to the participation of the Na-Ca exchanger in the Ca influx from the extracellular space. In addition, the results also suggest the possibility of an effect of Li on an additional Ca sensitive locus (different than the Na-Ca exchanger). In this connection, in isolated contractions lithium decreased the energy release fraction related to mitochondrial processes (H4) increasing the economy of the overall cardiac contraction.
