Sarcoplasmic reticulum calcium content fluctuation is the key to cardiac alternans.
The aim of this work was to investigate whether beat-to-beat alternation in the amplitude of the systolic Ca(2+) transient (Ca(2+) alternans) is due to changes of sarcoplasmic reticulum (SR) Ca(2+) content, and if so, whether the alternans arises due to a change in the gain of the feedback controlling SR Ca(2+) content. We found that, in rat ventricular myocytes, stimulating with small (20 mV) depolarizing pulses produced alternans of the amplitude of the Ca(2+) transient. Confocal measurements showed that the larger transients resulted from propagation of Ca(2+) waves. SR Ca(2+) content (measured from caffeine-evoked membrane currents) alternated in phase with the alternans of Ca(2+) transient amplitude. After a large transient, if SR Ca(2+) content was elevated by brief exposure of the cell to a Na(+)-free solution, then the alternans was interrupted and the next transient was also large. This shows that changes of SR Ca(2+) content are sufficient to produce alternans. The dependence of Ca(2+) transient amplitude on SR content was steeper under alternating than under control conditions. During alternation, the Ca(2+) efflux from the cell was also a steeper function of SR Ca(2+) content than under control. We attribute these steeper relationships to the fact that the larger responses in alternans depend on wave propagation and that wave propagation is a steep function of SR Ca(2+) content. In conclusion, alternans of systolic Ca(2+) appears to depend on alternation of SR Ca(2+) content. This, in turn results from the steep dependence on SR Ca(2+) content of Ca(2+) release and therefore Ca(2+) efflux from the cell as a consequence of wave propagation.
Díaz
Mary E
ME
Unit of Cardiac Physiology, School of Medicine, University of Manchester, UK. mary.e.diaz@man.ac.uk
O'Neill
Stephen C
SC
Eisner
David A
DA
D000200:Action Potentials; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000503:physiopathology; D020013:Calcium Signaling / Q000502:physiology*; D002304:Cardiac Pacing, Artificial; D025461:Feedback, Physiological; D006339:Heart Rate; D006352:Heart Ventricles; D008955:Models, Cardiovascular; D032383:Myocytes, Cardiac / Q000502:physiology* / Q000648:ultrastructure; D011674:Pulse; D051381:Rats; D017208:Rats, Wistar; D019837:Ryanodine Receptor Calcium Release Channel / Q000502:physiology; D012508:Sarcolemma / Q000502:physiology; D012519:Sarcoplasmic Reticulum / Q000502:physiology*
D019837:Ryanodine Receptor Calcium Release Channel