Action potentials propagate between adjacent cardiac myocytes through gap junctions
Cardiac muscle and its individual myocytes have a morphological character different from that of skeletal muscle and its cells (Fig. 9-12). Cardiac myocytes are shorter, branched, and interconnected from end to end by structures called intercalated disks, visible as dark lines in the light microscope. The intercalated disks connecting the ends of adjoining cardiac myocytes contain desmosomes (see p. 45) that link adjacent cells mechanically and gap junctions (see pp. 158–159) that link cells electrically. Cardiac muscle thus acts as a mechanical and electrical syncytium of coupled cells, unlike skeletal muscle fibers, which are separate cells bundled together by connective tissue. Like skeletal muscle, cardiac muscle is striated (see pp. 232–233) and its sarcomeres contain similar arrays of thin and thick filaments.
FIGURE 9-12 Electrical coupling of cardiac myocytes.
Contraction of cardiac muscle cells is not initiated by neurons as in skeletal muscle but by electrical excitation originating from the heart's own pacemaker, the sinoatrial node. When an action potential is initiated in one cell, current flows through the gap junctions and depolarizes neighboring cells, producing self-propagating action potentials. Beginning on page 483, we will consider cardiac electrophysiology in depth.
Cardiac myocytes receive synaptic input from autonomic neurons, but the sympathetic and parasympathetic divisions of the autonomic nervous system (see Chapter 14) use these synapses to modulate rather than to initiate electrical activity and contractile force of cardiac muscle.
Cardiac contraction requires Ca2+ entry through L-type Ca2+ channels
Whereas EC coupling in skeletal muscle does not require Ca2+ influx through L-type Ca2+ channels (see pp. 190–193), cardiac contraction has an absolute requirement for Ca2+ influx through these channels during the action potential. Cardiac myocytes have a T-tubule network similar to that of skeletal muscle myofibers except that a single terminal cisterna of the SR forms a dyad junction with the T-tubule rather than a triad junction. Furthermore, T-tubules of cardiac myocytes are located at the Z lines separating sarcomeres rather than at the A-I band junctions. Because the T-tubule lumen is an extension of the extracellular space, it facilitates the diffusion of Ca2+ from bulk extracellular fluid to the site of the L-type Ca2+ channels on the T-tubule membrane. Thus, the extracellular Ca2+ can simultaneously reach superficial and deep regions of the muscle. The increase in [Ca2+]i resulting from Ca2+ influx through the L-type Ca2+ channels alone is not, however, sufficient to initiate contraction. Rather, this increase in [Ca2+]i leads to an opening of the RYR Ca2+-release channels in the SR membrane. The resulting release of Ca2+ from the SR amplifies the rise in [Ca2+]i by a process known as Ca2+-induced Ca2+ release (CICR). Indeed, because the Ca2+-release channels remain open for a longer period than do L-type Ca2+ channels, the contribution of CICR to the rise in [Ca2+]i is greater than the flux contributed by the L-type Ca2+ channels of the T tubules. As noted above for skeletal muscle, single Ca2+-release events from local clusters of RYR1 channels—known as Ca2+ sparks—are the unitary events underlying EC coupling in cardiac muscle. N9-3 Summation of Ca2+spark/CICR events, initially activated by membrane depolarization, results in a wave of increased [Ca2+]i along the cell. N9-9
Propagation of the [Ca2+]i Wave in Cardiac Muscle
Contributed by Ed Moczydlowski
Although Ca2+ diffuses in the cytosol away from its SR release site, Ca2+ release at one site does not appear to be able to induce Ca2+ release from a neighboring SR Ca2+-release channel. Thus, Ca2+ release events are not propagated along the myocyte. In fact, the SR Ca2+-release channel does not appear to respond to generalized increases in cytoplasmic [Ca2+]i. Generalized cardiac muscle contractions occur as a result of the spatial and temporal summation of individual CICR events.
Beginning on page 522, we consider cardiac EC coupling in depth.
Cross-bridge cycling and termination of cardiac muscle contraction are similar to the events in skeletal muscle
Cardiac muscle is similar to skeletal muscle in the interaction of the actin and myosin during cross-bridge cycling, the resynthesis of ATP, and the termination of contraction. However, there are a few important differences. For example, the regulatory protein troponin C (see Fig. 9-6) of cardiac muscle (TNNC1) binds three Ca2+ ions per molecule versus the four for TNNC2 in skeletal muscle (see p. 237). More importantly, in cardiac muscle, SR Ca-pump activity is inhibited by the regulatory protein phospholamban (PLN). When PLN is phosphorylated by cAMP-dependent PKA, its ability to inhibit the SR Ca pump is lost. Thus, activators of PKA, such as the neurotransmitter epinephrine, may enhance the rate of cardiac myocyte relaxation. Beginning on page 522, we consider cardiac contraction and relaxation in depth.
In cardiac muscle, increasing the entry of Ca2+ enhances the contractile force
Whereas frequency summation and multiple-fiber summation are important mechanisms for regulating the strength of skeletal muscle contractions, these mechanisms would not be consistent with the physiological demands of cardiac muscle. Because cardiac muscle must contract only once with each heartbeat and must fully relax between each contraction, frequency summation is precluded. Furthermore, the extensive electrical coupling between cardiac myocytes, as well as the requirement that cardiac muscle contract homogeneously, eliminates the potential for multiple-fiber summation. Therefore, the strength of cardiac muscle contraction must be regulated by modulating the contractile force generated during each individual muscle twitch. This type of regulation is an important part of the adaptive response to exercise and is mediated by norepinephrine, a neurotransmitter released by the sympathetic nervous system.
The contractile function in cardiac muscle is regulated either by modulating the magnitude of the rise in [Ca2+]i or by altering the Ca2+ sensitivity of the regulatory proteins. Beginning on page 539 (see Tables 23-1 and 23-2), we discuss the modulation of these events by the autonomic nervous system (see Chapter 14).