In cardiac muscle, the junctional regions of the sarcoplasmic reticulum (SR) contain ryanodine receptors (RYRs) that are responsible for releasing calcium ions (Ca++) during an action potential. The RYR is a calcium channel that is activated by Ca++, allowing it to release a larger amount of Ca++ into the cytosol compared to the Ca++ entering from the sarcolemma. However, the release of Ca++ from the SR does not occur without the entry of a small amount of "trigger" Ca++. On the other hand, in skeletal muscle, the release of Ca++ from the SR is not dependent on the entry of Ca++ across the sarcolemma. Instead, it occurs due to a voltage-induced change in the dihydropyridine receptor (DHPR). This distinction in Ca++ release mechanisms is influenced by the isoform of DHPR present. If cardiac DHPR is expressed in skeletal muscle cells, the contraction of these modified cells will require extracellular Ca++.

In both skeletal and cardiac muscle, the interaction between actin and myosin is regulated by thin filaments, and an increase in intracellular Ca++ is necessary for actin-myosin binding. At low levels of intracellular Ca++ (<50 nmol/L), tropomyosin blocks the binding of myosin to actin. However, as the cytosolic Ca++ concentration rises during an action potential, Ca++ binds to troponin C, causing a conformational change in the troponin/tropomyosin complex. This change allows tropomyosin to move into the groove of the actin filament, exposing myosin binding sites on the actin filament. As long as the cytosolic Ca++ level remains elevated, myosin will bind to actin, undergo a ratchet action, and contract the cardiac muscle cell. This process is referred to as thin filament regulation of contraction, which is similar to skeletal muscle. In contrast, smooth muscle contraction is regulated by thick filaments.

During the rise in intracellular Ca++ and exposure of myosin-binding sites on actin, the myosin cross-bridges go through a series of steps that lead to contraction of the cardiac muscle cell. When at rest, the myosin molecules are energized, having partially hydrolyzed ATP to prepare for interaction with actin. An increase in intracellular Ca++ then exposes the myosin-binding sites on actin, allowing myosin to bind actin. The bound myosin undergoes a powerstroke, pulling the actin filament towards the center of the sarcomere. During this step, adenosine diphosphate (ADP) and inorganic phosphate (Pi) are released from the myosin head as ATP is utilized for muscle contraction. The myosin head moves approximately 70 nm with each ratchet action or cross-bridge cycle. The binding of ATP to myosin reduces its affinity for actin, causing myosin to detach from actin. Myosin then partially hydrolyzes the bound ATP to re-energize the head and prepare for another cycle. This four-step cycle is similar to the one described for skeletal muscle.
Figs. 13.1B 13.2 ). These junctional regions of the SR are enriched in ryanodine receptors (RYRs; a Ca++ release channel in the SR). The RYR is a Ca++-gated calcium channel, and so influx of Ca++ during an action potential is able to initiate release of Ca++ from the SR in cardiac muscle. The amount of Ca++ released into the cytosol from the SR is much greater than that entering the cytosol from the sarcolemma, although release of Ca++ from the SR does not occur without this entry of “trigger” Ca++ . In contrast, in skeletal muscle, release of Ca++ from the SR does not involve entry of Ca++ across the sarcolemma but instead results from a voltage-induced conformational change in the DHPR. Thus excitation-contraction coupling in cardiac muscle is termed electrochemical coupling (involving Ca++-induced release of Ca++), whereas excitation-contraction coupling in skeletal muscle is termed electromechanical coupling (involving direct interactions between the DHPR in the T tubule and the RYR in the SR). The basis for this difference in Ca++ release mechanisms appears to depend on the DHPR isoform because expression of cardiac DHPR in skeletal muscle cells results in a requirement for extracellular Ca++ for contraction of these modified skeletal muscle cells.
As in skeletal muscle, contraction of cardiac muscle is regulated by thin filaments, and an elevation in intracellular [Ca++] is necessary to promote actin-myosin interaction. At low (<50 nmol/L) intracellular [Ca++], binding of myosin to actin is blocked by tropomyosin. As cytosolic [Ca++] increases during an action potential, however, binding of Ca++ to troponin C results in a conformational change in the troponin/tropomyosin complex in which tropomyosin slips into the groove of the actin filament and exposes myosin binding sites on the actin filament. As long as cytosolic [Ca++] remains elevated, and hence myosin binding sites are exposed, myosin will bind to actin, undergo a ratchet action, and contract the cardiac muscle cell. Note that because myosin binding sites on actin are blocked at low [Ca++] and exposed during a rise in intracellular [Ca++], contraction of cardiac muscle is termed thin filament regulated. This is identical to the situation in skeletal muscle; in smooth muscle, in contrast, contraction is thick filament regulated (see
During a rise in intracellular [Ca++] and exposure of myosin-binding sites on actin, the myosin cross-bridges undergo a series of steps that result in contraction of the cardiac muscle cell. At rest, the myosin molecules are energized in that they have partially hydrolyzed adenosine triphosphate (ATP) to “cock the head” and are thus ready to interact with actin. An elevation in intracellular [Ca++] then exposes myosin-binding sites on actin and thus allows myosin to bind actin (step 1). The bound myosin subsequently undergoes a powerstroke in which the actin filament is pulled toward the center of the sarcomere (step 2). Adenosine diphosphate (ADP) and inorganic phosphate (Pi) are released from the myosin head during this step as the energy from ATP is used to contract the muscle. The myosin head moves approximately 70 nm during each ratchet action (cross-bridge cycle). Binding of ATP to myosin decreases the affinity of myosin for actin and thus allows myosin to release from actin (step 3). Myosin then partially hydrolyzes the bound ATP to reenergize (“cock”) the head (step 4) and ready the cross-bridge for another cycle. This four-step cycle is identical to that described for skeletal muscle (see
Fig. 12.13).