Comprehensive Physiology Wiley Online Library

Regulation of Cardiac Contraction by Calcium

Full Article on Wiley Online Library



Abstract

The sections in this article are:

1 Contractile and Regulatory Proteins of the Cardiac Myofibril
1.1 Myosin
1.2 Actin
1.3 Troponin
1.4 Tropomyosin
1.5 C‐Protein
2 Mechanical Properties of Myocardium
2.1 Isometric Tension
2.2 Shortening Velocity
2.3 Tension Transients
3 Regulation of Myocardial Contraction
3.1 Tension
3.2 Shortening Velocity
3.3 Kinetics of Tension Development and Relaxation
4 Conclusions
Figure 1. Figure 1.

Schematic representation of the spatial relationships of thick and thin filaments, titin, M‐line, and Z‐lines. Thick filaments are comprised primarily of myosin and a much smaller amount of C‐protein. Thin filaments are comprised primarily of actin, troponin, and tropomyosin.

Figure 2. Figure 2.

Schematic diagram of thick and thin filaments drawn approximately to scale. A‐actin, Tm‐tropomyosin, Tn‐troponin, LC2‐regulatory light chain (myosin light chain2), Alkali LC‐essential light chain (myosin light chain1). C‐protein (myosin binding protein C) is drawn in two different configurations because its position in the thick filament is not known .

Figure 3. Figure 3.

Ribbon representation of chicken gizzard skeletal muscle myosin subfragment‐1 looking into the narrow cleft that splits the central segment of the heavy chain. The heavy chain is displayed in different shades of gray to delineate the NH2‐terminal, central, and COOH‐terminal fragments that extend from residues Asp 4 Glu 204, Gly 216 Tyr 626, and Gln 647 Lys 843, respectively. These segments are separated by disordered loops in the x‐ray structure and were previously identified by mild tryptic cleavage of the myosin head as the 25, 50, and 20 kDa fragments, respectively ). These tryptic fragments are not independent folding domains; however, they are convenient for identifying large segments of the structure. Regulatory and essential light chains are labeled RLC and ELC, respectively.

Figure 4. Figure 4.

Crossbridge interaction cycle. A‐actin, M‐myosin, Pi‐inorganic phosphate, M*‐myosin that has undergone the transition to the force‐generating state.

Figure 5. Figure 5.

Velocity of shortening as a function of relative load. Vmax = maximum velocity of shortening, Po = maximum isometric tension.

Figure 6. Figure 6.

Cumulative force‐velocity (•) and power‐load (*) relationships obtained from eight single skinned cardiac myocytes. Data points in the force‐velocity relationship are means ± S. D. Mean force‐velocity data were fit using the normalized form of the Hill equation:where Vmax and Po, are maximum velocity of shortening and isometric force, respectively.

Figure 7. Figure 7.

Tension transient following rapid change in length of a single muscle fiber. Coincident with length change, tension decreases to a minimum (T1), which represents recoil of an elastic part of the crossbridge due to relative sliding of thick and thin filaments. Once the length change is complete, tension recovers to an intermediate value, T2, without detachment of the crossbridge from actin. This phase of force recovery is thought to be due to rotation of crossbridge heads. Thus, the total working distance of a crossbridge without detaching and reattaching is equivalent to the smallest imposed length changes (∼12 nm/half‐sarcomere) for which T2 is zero.

Idealized diagram based on data from Ford, et al.
Figure 8. Figure 8.

Determination of ktr in rabbit skinned psoas fibers. A: Schematic diagram of an experimental record showing the measured variables and the equation used for determining ktr. Once a fiber was steadily activated in a Ca2+‐containing solution and tension was constant (Fss), the fiber was slackened and tension was reduced to zero. Following a period of unloaded shortening, the fiber was rapidly reextended to its original length, thereby straining attached crossbridges and transiently increasing tension. The strained crossbridges then rapidly dissociated from actin, reducing tension to zero. The subsequent time‐course of tension recovery represents the redistribution of crossbridges from non‐tension‐generating to tension‐generating states. B: Actual record obtained during an experimental measurement of ktr at 15EC. The solid line is a computer‐fitted curve for which ktr was 18 s1. Sarcomere length was kept constant (±0.5 nm) by controlling the position of the first‐order line of a laser diffraction pattern obtained from the fiber.

From Metzger et al.
Figure 9. Figure 9.

Slack test plots from a skinned skeletal fiber at maximal (pCa 4.5, •) and submaximal (pCa 6.0, X) levels of activation. The insets show original recordings of length (upper) and tension (lower) at each pCa. The arrows indicate the time points at which tension redevelopment commenced, and the numbers indicate the corresponding points on the plots.

From Moss
Figure 10. Figure 10.

Schematic representation of thick and thin filaments showing possible mechanisms for slowing of Vmax at low levels of activation. Left: Representation of a slowly cycling cross‐bridge proposed to exist at low levels of activation, that has been carried beyond the normal configuration as a result of shortening. Further sliding of the thick and thin filaments beyond this point would be impaired by stretch of S‐2 and the overall rate of shortening would be slowed. Right: Cross‐bridge in the normal force‐generating configuration. If this cross‐bridge is long‐lived, continued shortening would result in a configuration similar to A. However, if this is a normally cycling cross‐bridge, further will cause compressive strain of S‐2 and detachment from actin before S‐2 buckles. In both cases, the accumulation of compressively strained or buckled cross‐bridges presumably depends on the rate of ADP dissociation from the A.M.ADP complex prior to the cross‐bridge detachment step.

From Hofmann et al.


Figure 1.

Schematic representation of the spatial relationships of thick and thin filaments, titin, M‐line, and Z‐lines. Thick filaments are comprised primarily of myosin and a much smaller amount of C‐protein. Thin filaments are comprised primarily of actin, troponin, and tropomyosin.



Figure 2.

Schematic diagram of thick and thin filaments drawn approximately to scale. A‐actin, Tm‐tropomyosin, Tn‐troponin, LC2‐regulatory light chain (myosin light chain2), Alkali LC‐essential light chain (myosin light chain1). C‐protein (myosin binding protein C) is drawn in two different configurations because its position in the thick filament is not known .



Figure 3.

Ribbon representation of chicken gizzard skeletal muscle myosin subfragment‐1 looking into the narrow cleft that splits the central segment of the heavy chain. The heavy chain is displayed in different shades of gray to delineate the NH2‐terminal, central, and COOH‐terminal fragments that extend from residues Asp 4 Glu 204, Gly 216 Tyr 626, and Gln 647 Lys 843, respectively. These segments are separated by disordered loops in the x‐ray structure and were previously identified by mild tryptic cleavage of the myosin head as the 25, 50, and 20 kDa fragments, respectively ). These tryptic fragments are not independent folding domains; however, they are convenient for identifying large segments of the structure. Regulatory and essential light chains are labeled RLC and ELC, respectively.



Figure 4.

Crossbridge interaction cycle. A‐actin, M‐myosin, Pi‐inorganic phosphate, M*‐myosin that has undergone the transition to the force‐generating state.



Figure 5.

Velocity of shortening as a function of relative load. Vmax = maximum velocity of shortening, Po = maximum isometric tension.



Figure 6.

Cumulative force‐velocity (•) and power‐load (*) relationships obtained from eight single skinned cardiac myocytes. Data points in the force‐velocity relationship are means ± S. D. Mean force‐velocity data were fit using the normalized form of the Hill equation:where Vmax and Po, are maximum velocity of shortening and isometric force, respectively.



Figure 7.

Tension transient following rapid change in length of a single muscle fiber. Coincident with length change, tension decreases to a minimum (T1), which represents recoil of an elastic part of the crossbridge due to relative sliding of thick and thin filaments. Once the length change is complete, tension recovers to an intermediate value, T2, without detachment of the crossbridge from actin. This phase of force recovery is thought to be due to rotation of crossbridge heads. Thus, the total working distance of a crossbridge without detaching and reattaching is equivalent to the smallest imposed length changes (∼12 nm/half‐sarcomere) for which T2 is zero.

Idealized diagram based on data from Ford, et al.


Figure 8.

Determination of ktr in rabbit skinned psoas fibers. A: Schematic diagram of an experimental record showing the measured variables and the equation used for determining ktr. Once a fiber was steadily activated in a Ca2+‐containing solution and tension was constant (Fss), the fiber was slackened and tension was reduced to zero. Following a period of unloaded shortening, the fiber was rapidly reextended to its original length, thereby straining attached crossbridges and transiently increasing tension. The strained crossbridges then rapidly dissociated from actin, reducing tension to zero. The subsequent time‐course of tension recovery represents the redistribution of crossbridges from non‐tension‐generating to tension‐generating states. B: Actual record obtained during an experimental measurement of ktr at 15EC. The solid line is a computer‐fitted curve for which ktr was 18 s1. Sarcomere length was kept constant (±0.5 nm) by controlling the position of the first‐order line of a laser diffraction pattern obtained from the fiber.

From Metzger et al.


Figure 9.

Slack test plots from a skinned skeletal fiber at maximal (pCa 4.5, •) and submaximal (pCa 6.0, X) levels of activation. The insets show original recordings of length (upper) and tension (lower) at each pCa. The arrows indicate the time points at which tension redevelopment commenced, and the numbers indicate the corresponding points on the plots.

From Moss


Figure 10.

Schematic representation of thick and thin filaments showing possible mechanisms for slowing of Vmax at low levels of activation. Left: Representation of a slowly cycling cross‐bridge proposed to exist at low levels of activation, that has been carried beyond the normal configuration as a result of shortening. Further sliding of the thick and thin filaments beyond this point would be impaired by stretch of S‐2 and the overall rate of shortening would be slowed. Right: Cross‐bridge in the normal force‐generating configuration. If this cross‐bridge is long‐lived, continued shortening would result in a configuration similar to A. However, if this is a normally cycling cross‐bridge, further will cause compressive strain of S‐2 and detachment from actin before S‐2 buckles. In both cases, the accumulation of compressively strained or buckled cross‐bridges presumably depends on the rate of ADP dissociation from the A.M.ADP complex prior to the cross‐bridge detachment step.

From Hofmann et al.
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Richard L. Moss, Scott H. Buck. Regulation of Cardiac Contraction by Calcium. Compr Physiol 2011, Supplement 6: Handbook of Physiology, The Cardiovascular System, The Heart: 420-454. First published in print 2002. doi: 10.1002/cphy.cp020111