A classical lay summary by Sarah L. Sturgill and Mark T. Ziolo, The Ohio State University, College of Medicine.
The heart needs to relax to properly pump blood. There are specific proteins in heart cells that control this relaxation. Previous work by Bassani and colleagues1 noticed a difference in the way these proteins work in rats and rabbits. One of the proteins, the sodium-calcium exchanger (NCX), acts like a door between the inside and outside of the cell and controls relaxation by allowing calcium, the ion that makes the heart contract, to leave the cell. There are differences in the job of NCX depending on the species. In larger mammals, such as rabbits, NCX is much more important to remove the calcium and cause relaxation. Smaller mammals, such as rats, do not need to use NCX as much1.
Since NCX plays a role in relaxation, a recent paper by Lotteau and colleagues2 studied heart cells in mice that did not have NCX. Since a mouse is a small mammal like a rat, NCX has a small role in relaxation. This is because only a very small amount of calcium leaves the cell. While there were some short-term changes in the calcium in these mice, the mice adapted and had normal heart function. However, these adaptations were not beneficial long-term and most of the mice died early. Even with the harmful adaptations, there were some good things that happened in these mice. They were protected from irregular heartbeats (i.e., arrythymias) and had less damage after a heart attack.
I believe if this experiment were performed in a larger mammal, such as a human, there would be different and even more harmful results. These studies demonstrate the importance of considering which animal species to use for heart research when trying to convert treatments to humans.
- Bassani JW, Bassani RA, Bers DM. Relaxation in rabbit and rat cardiac cells: species-dependent differences in cellular mechanisms. J Physiol. 1994;476(2):279-293. doi:10.1113/jphysiol.1994.sp020130
- Lotteau S, Zhang R, Hazan A, Grabar C, Gonzalez D, Aynaszyan S, Phillipson KD, Ottolia M, Goldhaber JI. Acute Genetic Ablation of Cardiac Sodium/Calcium Exchange in Adult mice: Implications for Cardiomyocyte Calcium Regulation, Cardioprotection, and Arrhythmia. Jour Am Heart Assoc. 2021;10(17). doi: 10.1161/JAHA.120.019273.