Related Experiment Videos
The determinants of contractility in the heart
1Department of Pharmacology, State University of New York, Syracuse 13210.
Insights
Cardiac contractility is primarily determined by calcium (Ca2+) and troponin C interactions, not dF/dt or dT/dt. Myocyte calcium handling regulates these interactions, influencing heart muscle contraction.
Area of Science:
- Cardiology
- Molecular Biology
- Physiology
Background:
- The heart's contraction-relaxation cycle involves complex myocyte interactions.
- Previous research sought an 'index' of contractility to integrate heart muscle studies.
Purpose of the Study:
- To challenge the use of dF/dt and dT/dt as sole indices of cardiac contractility.
- To propose calcium (Ca2+) and troponin C as the primary determinants of cardiac contractility.
Main Methods:
- Review of existing literature on heart muscle contraction.
- Analysis of data demonstrating paradoxical relationships between dT/dt and tension.
- Examination of Ca2+ handling mechanisms within myocytes.
Main Results:
- dF/dt and dT/dt do not reliably indicate cardiac contractility.
- Increasing dT/dt can paradoxically correlate with lower tension.
- Decreasing dT/dt can occur with increased contractile tension.
Conclusions:
- Cardiac contractility is principally governed by Ca2+ interactions with troponin C.
- dT/dt reflects a dynamic equilibrium of Ca2+ binding.
- Myocyte Ca2+ handling acts as a feedback system regulating contractility.
Abstract:
The contraction-relaxation cycle of the heart represents the combined action of a variety of different components of the myocytes. For many years an 'index' of contractility has been sought as a means of describing and integrating the large amount of information available from the studies of heart muscle contraction. This review will undertake to show that dF/dt, recorded from the whole heart, and dT/dt, recorded in isometric studies of isolated heart muscle preparations, should not be considered as the 'index' of contractility. Examples will be presented in which an increasing dT/dt is paradoxically accompanied by a lower tension, while a decreasing dT/dt can occur concomitantly with an increased contractile tension. Arguments are further presented in support of the concept that Ca2+, in conjunction with troponin C, is the main determinant of cardiac contractility and that dT/dt reflects a dynamic equilibrium between free and troponin-bound Ca2+. Peak tension is thus the net result of overlapping events competing for Ca2+ during the latter part of contraction, that is, during Phase II of contraction as defined below. These suggestions are based upon the following considerations: (a) The Ca2+ pumps are active even during rest and serve to maintain low cytosolic Ca2+ levels. (b) As cytosolic Ca2+ concentration increases, Ca2+ pump activity also increases. (c) In addition, the Na+/Ca2+ exchange is activated by elevated Ca2+ concentrations and serves to decrease cytosolic Ca2+ levels. (d) The net result is a decline in free Ca2+ concentration during Phase II and a reduction in the rate of cross-bridge formation until peak tension is reached. Thus, the Ca2+ handling elements of the myocyte serve as a finely tuned feedback device, regulating troponin C-Ca2+ interactions controlling the Ca2+ concentration of the cytosol and as a result, the actin and myosin interaction. Factors which influence the function of these elements will change the contractility of the heart.